Osteotropic drug delivery system (ODDS) based on bisphosphonic prodrug. V. Biological disposition and targeting characteristics of osteotropic estradiol

An osteotropic drug delivery system (ODDS) based on a bisphosphonic prodrug has been developed for 17 beta-estradiol (E2) to improve patient compliance in estrogen replacement therapy of postmenopausal osteoporosis. The biological disposition and the targeting efficiency of a bisphosphonic prodrug of E2, disodium [17 beta-(3'-hydroxy-1',3',5'-estratrienyloxy)carbonylpropyl carboxamidomethylene]bisphosphonate (E2-BP), was investigated in ovariectomized rats. After intravenous injection, E2-BP was rapidly taken up into the bone and subsequently cleared from the bone at a half-life of 13.5 d. The bone concentration of regenerated E2 was maintained throughout 28 d. In contrast, E2 injected intravenously showed extremely low bone distribution and rapid clearance from the bone, and E2 administered orally showed even lower bone distribution. Therapeutic availability (TA) and drug targeting index (DTI), which were calculated on the basis of the AUCs for E2 in the bone and plasma after injection of E2-BP and E2, were 64.6 and 451, respectively. These results suggest that ODDS has a potential to improve not only the apparent potency but also the therapeutic index of E2. As compared with the conventional estrogenic products, E2-BP should improve patient compliance with lower adverse effects and less frequent medication in long-term estrogen replacement therapy.     

Oxygen pressure measurements of silica saturated Fe-O-SiO2 melts by the EMF method using zirconia solid electrolyte

The thermodynamic properties of silica-saturated iron silicate slags have been studied from oxygen partial pressure measurements using a solid electrolyte galvanic cell. The oxygen activity in molten silver bath equilibrated with iron silicate slags was determined by the following cell type, Pt, NiNiOJO= /slag-Ag(O), LaCrO₃, Pt at temperatures between 1473 and 1573 K for the slags ranging in compositions from iron saturation to magnetite saturation. The oxygen partial pressures obtained in this investigation were in good agreement with those given by the previous study using the CO-CO₂ gas equilibrium method. The data showed that the Fe^{+ ++}/Fe⁺⁺ ratio is proportional to . Formerly Graduate Students, Kyoto University     

Bloch wave-based calculation of imaging properties of high-resolution scanning confocal electron microscopy

An efficient, Bloch wave-based method is presented for simulation of high-resolution scanning confocal electron microscopy (SCEM) images. The latter are predicted to have coherent nature, i.e. to exhibit atomic contrast reversals depending on the lens defocus settings and sample thickness. The optimal defocus settings are suggested and the 3D imaging capabilities of SCEM are analyzed in detail. In particular, by monitoring average image intensity as a function of the probe focus depth, it should be possible to accurately measure the depth of a heavy-atom layer embedded in a light-element matrix.     

Effect of crosslinked structure on SO2 gas sorption properties in amino‐functional copolymers

SO₂ gas sorption properties were examined for poly(styrene‐co‐chloromethyl styrene) functionalized with N,N‐dimethyl‐1,3‐propanediamine (DMPDA). The DMPDA‐functional copolymers were prepared under various reaction conditions. Two types of SO₂ sorption behaviors were observed for these DMPDA‐functional copolymers: SO₂ sorption capacity was very high irrespective of slow sorption/desorption rates (type I), and the sorption/desorption rates were very fast while SO₂ sorption capacity was small (type II). Fourier transform infrared analysis and dielectric loss measurement revealed that the type II sorption behavior was obtained for the highly crosslinked DMPDA‐functional copolymers. The degree of crosslinking was affected by both the solvent used to react DMPDA with the copolymer and the percent conversion of the chloromethyl styrene group. It was confirmed that DMPDA‐functional copolymers having a highly crosslinked structure are suitable materials in quartz crystal microbalance (QCM)‐type polymeric SO₂ gas sensors. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 2982–2987, 2003     

Thermal and mechanical properties of tetramethyl-p-silphenylenesiloxanedimethylsiloxane block copolymer

Several kinds of $\text{tetramethyl}\text{-p-}\text{silphenylenesiloxane}\text{dimethylsiloxane}$ (TMPS/DMS) block copolymers having various compositions and segment lengths were synthesized by the polycondensation of p-bis(dimethylhydroxysilyl)benzene and silanol-terminated DMS oligomers of different degrees of polymerization, which were 19, 43, 300, 380 and 540 DMS monomer units. The compositions ranged from TMPS/DMS wt% ratio of 100/0 to 24/76. For these copolymers, differential scanning calorimetry was carried out to determine the melting temperatures, the heat of fusion and the crystallinities. The melting temperatures and the crystallinities of the block copolymers were found to decrease as DMS contents were increased from 11 to 76 wt% and as DMS segment lengths were decreased from 540 to 19. The crystalline parts of TMPS segment would be increased according to the long TMPS sequences which were obtained from the copolymerizations by using DMS oligomers with high degrees of polymerization such as 300, 380 and 540. The stress-strain behaviour and the dynamic mechanical behaviour were also investigated for these copolymers. The tensile strength was decreased and the percentage elongation was increased with increasing DMS content and segment length. In the case of the copolymers for which the DMS contents remained constant at 26 wt%, two major transitions were observed at around ?120° and ?10°C for the copolymers having DMS block sizes of 300, 380 and 540. But for the copolymers having those of 19 and 43 the two transitions merged together at ?50°C. The relaxations at ?120°C corresponding to the glass transition of DMS component and those at ?10°C are due to the amorphous TMPS phase which is separated from the DMS phase owing to the longer sequence length. The relaxation observed around ?50°C is due to the shorter sequence length of TMPS in the main chain plus the presence of more flexible DMS component. It may be suggested that the long sequence length causes large domains of hard and soft phases which consist of TMPS and DMS blocks respectively.     

Transition of the lubricated wear of carbon steel

To study the transition of the lubricated wear of 0.53% C steel in the steady state, wear tests were carried out by rubbing the annular surfaces of two cylindrical test pieces in machine oil with no additives. The ratio of mating areas was varied to approach actual contact conditions. Three regions of variation in the coefficient of friction with contact load were determined. Fatigue wear, characterized by a friction coefficient μ ≈ 0.05 and a specific wear rate ω_s ≈ 0.005 × 10^?6 mm³ N^?1 m^?1, occurs in the first region.A transition from fatigue wear to adhesive wear, with μ ≈ 0.05?0.12 and ω_s ≈ (0.005?0.05) × 10^?6 mm³ N^?1 m^?1, takes place gradually within a specific load range. Finally, adhesive wear predominates above the load level that marks the end of the transition. The same behaviour was analysed through stepwise loading tests. The onset of transition and seizure occurs at constant mean surface temperatures. However, the end of transition is also affected by factors other than temperature. The results are compared with the transitions reported by the International Research Group on Wear of Engineering Materials of the Organization for Economic Cooperation and Development.     

n- and p-Channel field-effect transistors based on diquinoxalinoTTF derivatives

Three new quinoxalinoTTF derivatives with methyl, trifluoromethyl and fluoro groups were synthesized and characterized by UV–vis absorption spectroscopy, differential scanning calorimetry, X-ray single crystal analysis, X-ray diffraction, and field-effect transistor (FET) characteristics. All of them have π-stacking structures in the single crystals. The quinoxalinoTTF derivative with trifluoromethyl groups exhibited an n-type FET, which is a rare example of n-channel FETs based on TTF derivatives. The highest electron mobility is 0.01 cm² V^?1 s. The FET polarity was converted to p-channel from n-channel by replacing the trifluoromethyl groups with methyl groups. The hole mobility is as high as 0.2 cm² V^?1 s. In contrast, the fluoro substituted derivative did not show FET properties due to the poorly ordered molecular arrangement.     

Large-scale atomistic modeling of nanoelectronic structures

Large-scale molecular-dynamics simulations are performed on parallel computers to study critical issues on ultrathin dielectric films and device reliability in next-decade semiconductor devices. New interatomic-potential models based on many-body, reactive, and quantum-mechanical schemes are used to study various atomic-scale effects: growth of oxide layers; dielectric properties of high-permittivity oxides; dislocation activities at semiconductor/dielectric interfaces; effects of amorphous layers and pixellation on atomic-level stresses in lattice-mismatched nanopixels; and nanoindentation testing of thin films. Enabling technologies for 10 to 100 million-atom simulations of nanoelectronic structures are discussed, which include multiresolution algorithms for molecular dynamics, load balancing, and data management. In ten years, this scalable software infrastructure will enable trillion-atom simulations of realistic device structures with sizes well beyond μm on petaflop computers     

Intracerebroventricular administration of mouse leptin does not reduce food intake in the chicken

Recently, it has been suggested that leptin plays an important role in regulation of food intake and metabolism in rats and mice, however, the effect of central administration of leptin on food intake in chicks has not been reported. We have investigated the anorexigenic effect of leptin administered by intracerebroventricular (i.c.v.) injection in chicks using mouse leptin, which shows 97% homology to chicken leptin. Three experiments were conducted. After being deprived of food for 3 h, male broiler chicks were administered leptin by i.c.v. injection at dose levels of 0, 0.2, 1.0 and 5.0 microg (Experiment 1) or 0, 2.5 and 5.0 microg (Experiment 2). The birds were allowed free access to the diet for 2 h (Experiment 1) and 24 h (Experiment 2) after treatment. Male Single Comb White Leghorn chicks were used in Experiment 3 and were treated in the same manner as in Experiment 1. In all experiments, central administration of mouse leptin did not influence food intake in the time periods examined. It appears that either mouse leptin does not bind to the chicken leptin receptor or in the chicken brain the leptin receptor may be absent.     

A rotary encoder based on magneto-optical storage

A new kind of the rotary encoder based on the magneto-optical (MO) storage is proposed. Using the MO methods, a small high-precision high-response rotary encoder can be realized. High precision is achieved by a two-stage process in which the code disk is firstly written using the direct transfer recording, and then rewritten using the corrections based on the measured errors. The systems for writing to, reading from, and evaluating the MO encoder are developed, with the optimal MO encoder reading and writing parameters determined experimentally. A trial MO encoder with a resolution of 9000 pulses/revolutions is created directly from a reference encoder, delivering an accuracy of approximately 2.8 in. The maximum resolution and response frequencies achieved are 18000 p/r and 400 kHz. After the corrected transfer recording, accuracies of 1.3 in at a resolution of 2250 p/r and 1.7 in at 9000 p/r are achieved.