Agenda

Baclofen, a GABAB agonist, has been used to treat muscle stiffness in patients with multiple sclerosis or cerebral palsy. We found that baclofen decreased food intake and body weight in obese animals such as db/db and diet-induced obesity mice. The effects of baclofen on food intake and body weight were unique in that it had significant effects only in obese subjects but not in lean control. In order to see whether baclofen could reduce body weight in obese patients, we have been conducting a clinical study. Nine obese subjects whose BMI is 30 kg/m2 or more have been enrolled in the study so far. They had baclofen three times a day for 12 weeks. The amount of baclofen was 15 mg/day at the beginning and increased up to 30 mg/day in 10 days, as in patients with muscle stiffness. The body weight as well as waist circumference was significantly decreased at 12 weeks compared to the baseline values. The serum leptin levels, which could reflect the amount of adipose tissues, were also decreased at 12 weeks. The analyses with visual analogue scale showed that appetite was also decreased by baclofen. There were no adverse effects. These data suggest that GABAB agonists could be used as a new therapeutic reagent for obesity.

The renin-angiotensin system plays a pivotal role in regulating blood pressure and is involved in the pathogenesis　of kidney disorders and other diseases. Here, we report that the growth factor midkine is what we believe　to be a novel regulator of the renin-angiotensin system. The hypertension induced in mice by 5/6 nephrectomy　was accompanied by renal damage and elevated plasma angiotensin II levels and was ameliorated by an　angiotensin-converting enzyme (ACE) inhibitor and an angiotensin receptor blocker. Notably, ACE activity　in the lung, midkine expression in the lung, and midkine levels in the plasma were all increased after 5/6　nephrectomy. Exposure to midkine protein enhanced ACE expression in primary cultured human lung microvascular endothelial cells. Furthermore, hypertension was not induced and renal damage was less severe in　midkine-deficient mice. Supplemental administration of midkine protein to midkine-deficient mice restored　ACE expression in the lung and hypertension after 5/6 nephrectomy. Oxidative stress might be involved in　midkine expression, since expression of NADH/NADPH oxidase–1, –2, and –4 was induced in the lung after　5/6 nephrectomy. Indeed, the antioxidative reagent tempol reduced midkine expression and plasma angiotensin　II levels and consequently ameliorated hypertension. These results suggest that midkine regulates therenin-angiotensin system and mediates the kidney-lung interaction after 5/6 nephrectomy.

This technology provides a neuronal cell death inhibitor comprising a compound having an inhibitory activity on the production and/or release of glutamic acid in a microglia. By inhibiting the production and/or release in a microglia, neurite bead-like degeneration or neuronal cell death can be inhibited. The compounds include glutaminase inhibitor and gap-junction inhibitor. Both inhibitors successfully suppressed disease progression of animal models for cerebral infarction, autoimmune encephalomyelitis, amyotrophic lateral sclerosis (ALS), and Alzheimer’s disease in vivo.

With the screening method, we have synthesized several compounds using above inhibitors as lead compounds. These compounds could be candidates for treating neuronal degeneration in a variety of neurological disorders.

Amyloid-protein (A) oligomers may be the proximate neurotoxins in Alzheimer’s disease (AD). We designed short peptides using spot-synthesized peptide array of KLVFF derivatives (which is the critical region in amyloid fibril formation). The designed peptides affected early aggregation of Aß1-42, decreased neurotoxicity, and increased the object recognition memory of Aß1-42-injected mice in the novel object recognition test. Our results provide significant insights into strategies for developing therapeutics for AD. The designed peptides could increased early aggregation of Aß and provide positive effect by decreasing the occurrence of Aß-oligomers. The technology can be used for the definitive treatment of Alzheimer’s disease.

Researchers at Gifu University have discovered novel anti-prion compounds and successfully optimized their chemical structures. They have established the methods for organic synthesis of those optimized compounds.

The lymphatic system possesses numerous active pumps to propel lymph to the central lymphatic systems. Decreased pumping activity may be associated with lymphedema. However, there were no non-invasive methods to measure lymphatic pump force in clinical practice. We introduce a new method to measure lymphatic pumping and compared the activity between healthy and lymphoedematous legs using Indocyanine green (ICG) fluorescence lymphography.

This technology provides a novel promoter that is induced by pathogen infection. Gene transfer using the present promoter allows creation of transgenic plant wherein a desired gene is expressed specifically on the occasion of pathogen infection. Accordingly, by transferring any gene involved in protective response, pathogen-resistant plant can be created which evokes a prompt protective response to pathogen infection.

Vortex generator (VG) is a device designed to delay or prevent flow separation by generating vortexes and mixing a flow. Some types of VGs are necessary only in take-off and landing, but generate drag in steady cruise conditions. Smart Vortex Generator (SVG) is a new VG concept, where VG autonomously transforms its position between a vortex-generating position in take-off and landing and a drag-reducing position in steady cruise conditions, without any energy supply, by utilizing functions of shape memory alloy and approximately 70K difference in ambient temperature between the ground and the cruise altitude.

This technology has realized high quality 3C-SiC bulk crystal using solution growth with multi-component solvent developing multi-function. 3C-SiC crystals were spontaneously grown from the Si solvent in a large temperature gradient to improve the yield of crystals, and quality of the grown crystals was characterized.

A new RTV silicone is eco-friendly because this technology differs from the previous technology adopting toxic tin organic compounds as a hardening agent in that we employ a new hardening one.

To provide a system and program for estimating arteriosclerosis, method for creating three dimensional moving image of blood vessel using multi-channel ultrasonic probe and method for measuring diameter variation with time due to pulsate flow and method for estimating mechanical properties such as stiffness, strength, and critical burst pressure of the wall of blood vessel are given.

This new surgical navigator is a completely frameless and markerless system, features semi-automatic registration without direct contact with patients, and updates registration and tracking information when patients move.

Researchers at Nagoya University have developed a novel endoscope support system that fuses real endoscopic images and virtual 3-D images generated via CT or MRI. Real images via endoscope are displayed on the left half of the screen and corresponding virtual images on the right. By synchronizing real and virtual images on the screen, various information, such as spatial relation, that a conventional system does not provide can be obtained. Ancillary images and information are also displayed on the screen at the same time to support diagnostics.

New 3-dimensional universal external fixator offers an 3 dimensional external fracture fixation system comprising of light-weighted, cheap and X-ray permeable connecting devices and titanium rod. The device is extremely light in weight, but still offers incredibly rigid fixation.

New device to treat hand and foot swelling is very light, low-priced therapeutic device to treat swollen hands and feet caused by inflammatory diseases or injury to the hand.

Researchers at Nagoya University have developed a novel method to create Multifunctional Envelope -Type Nanodevices. Adopting micro-fluidic approach, this on-chip based method realized simple, rapid, cost-effective fabrication of MEND than conventional methods. It takes less than 1/2 hour to create MEND while conventional method takes up to 2 days.

Researchers at Nagoya University discovered a novel way to deliver genes to intact plant cells via Carbon Nanotube technology. Cup-Stack Carbon Nanotube (CSCNT: length ~2 micron meter and diameter ~100 nano meter) coated with cellulase (cell wall degrading enzyme) creates nano-holes in the cell walls; seeps into the interior of the cell; penetrates the nuclear membrane; and delivers genes into the cell nucleus. This method realizes high transfection efficiency as much as 6% without any major cell damage and can be applied to a variety of plant cells.

Researchers at Nagoya Institute of Engineering have found a new adhesive nanofiber consisting of trimeric autotransporter adhesin (TAA) on a cell surface of a highly adhesive bacterium, Acinetobacter sp. Tol 5. Unlikely to other TAAs already reported this new TAA is responsible for nonspecific adhesion to abiotic surfaces and cell aggregation. Our finding is applicable to controlling bacterial adhesion and immobilization of industrial microbes.

A system for high speed counting of airborne bio-particles (BPs) is proposed. It consists of electrostatic precipitation (ESP) to enhance trapping of BPs, dielectric barrier discharge (DBD) to break the cell wall, and detection of the DNA after blotting on a membrane filter. This system can be applied to a variety of indoor environments including hospitals, pharmaceutical or food processing companies.

Malaria is one of the most serious parasitic infections. More than 300 million people are infected by malaria parasite and 2.7 million are estimated to be dead. Additionally, the appearance of strains resitant to commercially available antimalarial drugs makes the search for new antimalarials a global demand.

When malaria parasites use hemoglobin of the infected patients as a source of nutrients and energy, detoxification through polymerizing heme is an essential process for their life since they produce heme which is harmful to themselves. Recently, it became clear that antimalarial drugs, like chloroquin, acquire the medicinal effect through the inhibition of heme polymerization. Therefore we designed new molecules which are expected to have higher heme affinity as potential antimalarial drugs. Among the compounds we synthesized, several compounds had high antimalarial activities (EC50: 10-8 -10-9 M) as well as low toxicities toward mammalian cells.

Researchers at UNC Chapel Hill have developed a photomanipulation method that　allows for reversible and reproducible activation of ‘caged’, or inactive proteins. The method is genetically encoded and allows for site-specific modulation of protein activity with precisely controlled kinetics. In this manner, the technique described here greatly improves utility over existing protein investigation methods.

Researchers at NC State have developed porous nanocellular foam structures, based on starches modified from renewable natural polymers, having numerous possible commercial applications. Currently, there is increasing interest in replacing inorganic fillers in paper, coatings, and plastics with organic renewable fillers, such as starches, to improve the economics, performance, and environmental aspects of these products. The disclosed nanoparticles prepared from organic, renewable starches have unique properties including significantly increased specific surface area, high degree of brightness and opacity, light weight, and porosity which can be used in a number of mechanisms for the storage and gradual release of suitable compounds. These nanoparticle starches can be altered to have a hydrophobic or hydrophillic character depending on processing techniques. The porous nature of the particles will allow them to be used in applications such as the delivery of drugs and pesticides, encapsulation of volatile compounds, use as guest particles, and use in the production of lightweight concrete.