Intermittent administration of brain-derived neurotrophic factor (BDNF) ameliorates glucose metabolism and prevents pancreatic exhaustion in diabetic mice

We previously demonstrated that repetitive administration of brain-derived neurotrophic factor (BDNF) ameliorates glucose metabolism and energy expenditure in obese diabetic db/db mice. However, we have not evaluated in detail the effect of single or intermittent BDNF administration on glucose metabolism in a diabetic animal model. The objectives of this study were to examine the dose-response effect and dosing interval of BDNF administration in db/db mice and to evaluate the effect of intermittent BDNF administration on pancreatic function in db/db mice. We evaluated the dose-response effect of BDNF by single administration in db/db mice. First, single administration of BDNF greater than 70 mg/kg significantly reduced blood glucose concentration one day after administered, and the BDNF effect was maintained for 6 d. Next, the effects of BDNF administered twice a week at 4, 10, 25, and 62.5 mg/kg on blood glucose concentration, and the effects of BDNF administered once a week at 10, 20, 30, 50, and 70 mg/kg on blood glucose concentration were examined in db/db mice. In the intermittent treatment studies, BDNF dose-dependently ameliorated glucose metabolism by not only the twice-a-week administration but also the once-a-week administration. Lastly, because BDNF reduces the food intake of obese hyperphagic diabetic mice, the effects of BDNF administered once or twice a week on the blood glucose concentration and plasma and pancreatic insulin concentrations in db/db mice were compared with those of the vehicle under pair-fed conditions. Under pair-fed conditions, the intermittent administration of BDNF (25 mg/kg, twice a week, or 50 mg/kg, once a week) significantly reduced the blood glucose concentration and increased the plasma and pancreatic insulin concentrations compared with those in the pair-fed vehicle-treated db/db mice. This indicates that the prolonged hypoglycemic effect of BDNF is not simply due to the reduction of food intake. In conclusion, we demonstrated that the intermittent administration of BDNF ameliorates glucose metabolism and prevents pancreatic exhaustion in obese diabetic mice. These findings indicate that BDNF may have potential as a unique hypoglycemic agent for the treatment of diabetes at a fundamental level with good patient compliance.     

Isolation and characterization of the Shiga toxin gene (stx)-bearing Escherichia coli O157 and non-O157 from retail meats in Shandong Province, China, and characterization of the O157-derived stx2 phages

Infection by Shiga toxin (Stx)-producing Escherichia coli of non-O157 and O157 serotypes are rare in China, but infection by O157 serotype was found in Shandong Province and three other provinces in China. To understand the reason for these rare infections and to determine the safety of retail meats in Shandong Province, we examined the distribution of Shiga toxin gene (stx)-bearing E. coli in retail meats and characterized the isolated stx-bearing strains. We used hybridization with DNA probes and isolated stx1- and/or stx2-positive E. coli from 31 (58%) of 53 retail meat samples, with beef showing the highest frequency (68%). Of 42 stx-positive isolates, none belonged to O157. Using the O157-specific immunomagnetic bead technique, we isolated E. coli O157 carrying the eae and stx2 genes from eight beef samples (26%). These strains produced little or no Stx2 and carried a unique q gene. Replication of the stx2 phages was detected in these strains, whereas stx2 phage replication was not detected in our previous study in which we examined similar stx2-bearing E. coli O157 strains from other Asian countries. Analysis of E. coli C600 lysogenized with the stx2 phages found in this study suggests that the lack of Stx2 production is due to changes in non-q gene region(s) of the phage genome or chromosomal mutation(s) in the host. Our data and reports by other workers suggest it is necessary to determine if various stx2-bearing E. coli O157 strains producing Stx2 to varying degrees are distributed in meats in various locations in China.     

Metabolic disturbance of tryptophan-nicotinamide conversion pathway by putative endocrine disruptors, bisphenol A and styrene monomer

Bisphenol A, a monomer of polycarbonate plastics, disturbed the conversion pathway of the amino acid tryptophan to the vitamin nicotinamide. The conversion ratio of tryptophan to nicotinamide was reduced to 1/15 by feeding a diet containing 1% bisphenol A. A putative disturbing reaction is kynurenine-->3-hydroxykynurenine, which is catalyzed by kynurenine monohydroxylase. This is an FAD-enzyme and requires NADPH as a coenzyme. Styrene monomer (1% addition to a normal diet) did not affect the food intake or the body weight, but slightly reduced the conversion ratio of tryptophan-nicotinamide.     

Correlation between friction of articular cartilage and reflectance intensity from superficial images

The lubrication mechanism of articular cartilage is characterized by an efficient performance. In this work, friction of articular cartilage was evaluated with in-site images of articular surface. The images were captured with the laser light reflected at the interface between a prism and articular cartilage. The attenuation of reflectance was associated with the increase of the contact of collagen network of articular cartilage. The light reflectance and friction coefficient for short sliding presented a significant positive correlation. Friction tests were also carried out for short (30 s) and long (300 s) preloading times. The results indicate that depletion of fluid film is responsible for the increase of friction and the recovery of the fluid film was observed for the long preloading after the early stage of sliding.     

Phase reaction and diffusion path of the SiC/Ti system

Bonding of SiC to SiC was conducted using Ti foil at bonding temperatures from 1373 to 1773 K in vacuum. The total diffusion path between SiC and Ti was investigated in detail at 1673 K using Ti foil with a thickness of 50 μm. At a bonding time of 0.3 ks, TiC at the Ti side and a mixture of Ti₅Si₃C _x and TiC at the SiC side were formed, yielding the structure sequence of β-Ti/Ti+TiC/Ti₅Si₃C _x +TiC/SiC. Furthermore, at the bonding time of 0.9 ks, a Ti₅Si₃C _x layer phase appeared between SiC and the mixture of Ti₅Si₃C _x and TiC. Upon the formation of Ti₃SiC₂ (T phase) after the bonding time of 3.6 ks, the complete diffusion path was observed as follows: β-Ti/Ti+TiC/Ti₅Si₃C _x +TiC/Ti₅Si₃C _x /Ti₃SiC₂/SiC. The activation energies for growth of TiC, Ti₅Si₃C _x , and Ti₃SiC₂ were 194, 242, and 358 kJ/mol, respectively.     

Intramolecular triplet energy migration in poly(2-vinylnaphthalene) and poly(naphthylalkyl methacrylate)s in solid solution: Effects of side chain length

Summary The effect of side chain length on intramolecular triplet energy migration of naphthalene containing polymers was investigated by a delayed fluorescence (DF) spectroscopy for the solid solution of the polymers. The degree of triplet energy migration depends strongly on whether the chromophores are directly attached to the main chain or not.     

Effect of fluid motion on radiation-induced polymerization of ethylene in a tubular reactor

The influence of the turbulence of reactant on the radiation-induced polymerization of ethylene in 40 mole-% Freon-114 (C₂Cl₂F₄) was studied using a tubular reactor at 400 kg/cm² and 25°C with a dose rate of 1.3 × 10⁵ rad/hr. At constant linear velocity and tube diameter, the polymer concentration was shown to increase linearly with the reactor tube length. This indicates that the polymerization is in a stationary state. By changing the linear velocity from 3.5 to 42.7 cm/sec and the tube diameter from 5 to 14 mm, the space time yield and the molecular weight of polymer were found to vary between 0.21 and 0.46 mole ethylene/1.-hr and from 5.0×10³ to 10.5×10³, respectively. The space time yield and molecular weight decreased sharply to about one half those in the static polymerization with increasing fluid turbulence and then slowly increased in the highly turbulent state. Similar effects were observed in a tank reactor when the stirring speed was changed.     

Preparation of modified poly(vinyl chloride) containing N,N-di(β-hydroxyethyl)dithiocarbamate and its reaction with metal ions

Reaction of N,N-di(β-hydroxyethyl)dithiocarbamate ion with poly(vinyl chloride) (PVC) was undertaken, and the reaction with metal ions of the polymer obtained was investigated. The effect of γ-irradiation on the reaction with metal ion was also studied. The modified PVC (PHDC) obtained from the reaction with N,N-di(β-hydroxyethyl)dithiocarbamate ion is pale yellow even after reaction at 100°C for 5 hr in dimethylformamide (DMF); it is soluble in dipolar solvents and its chlorine content is decreased considerably. This polymer reacted well with acetate salts of copper(II), nickel(II), zinc(II), and silver(I) heterogeneously in aqueous solution because of the introduction of hydrophilic groups (two hydroxy groups). The reactivity of the metal ions toward the polymer was of the order Ag(I) ? Cu(II) > Ni(II) > Zn(II). From the result of the reaction of γ-irradiated polymer with cupric ion, the polymer was judged to have fairly good antiradiation property.     

Synthesis of terpene alcohols from isoprene oligomers

Various terpene alcohols were prepared from isoprene oligomers via two steps: epoxidation with peracetic acid and isomerisation with aluminium triisopropoxide. For example, 2-methylene-6-methyl-7-octene-1-o1 was prepared from 2,6-dimethyl-1,7-octadiene. From 2,6-dimethyl-2,7-octadiene, 3,3,6-trimethyl-1,5-heptadiene, 2,7-dimethyl-2,6-octadiene, 2,6-dimethyl-1,3,6-octatriene, 1-methyl-4-isopropenyl-1-cyclohexene, and 1,5-dimethyl-1,5-cyclooctadiene, the corresponding alcohols were obtained, respectively.     

Liquefaction of subbituminous coals under apparently non-hydrogenative conditions

Reactivities of several coals of different ranks have been examined in degrading extractions with aromatic solvents under apparently non-hydrogenative reaction conditions. Pyrene and A240 pitch liquefied the fusible coals in high yields and the slightly-fusible coals in moderate yields, indicating the importance of fusibility in such liquefaction processes. A240-LS pitch is a powerful solvent for slightly-fusible coals. Considerable amounts of pyridine- or THF-soluble fractions were produced especially with A240-LS pitch. A240 pitch is a better solvent than pyrene for some slightly-fusible coals. However, the extent of depolymerization of liquefied coal, pyridine- or THF-solubility, was definitely inferior. Yields of such fractions are higher for lower-rank coals. The mechanism of coal liquefaction under apparently non-hydrogenative conditions is discussed with emphasis on the stabilization of thermal fragments derived from the coal.