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71.
Fumihiko Maekawa Okiru Komine Katsushige Sato Tomoyuki Kanamatsu Motoaki Uchimura Kohichi Tanaka Hiroko Ohki-Hamazaki 《BMC neuroscience》2006,7(1):1-13
Background
Results of the Women's Health Initiative Memory Study (WHIMS) raised concerns regarding the timing and formulation of hormone interventions. Conjugated equine estrogens (CEE), used as the estrogen therapy in the WHIMS trial, is a complex formulation containing multiple estrogens, including several not secreted by human ovaries, as well as other biologically active steroids. Although the full spectrum of estrogenic components present in CEE has not yet been resolved, 10 estrogens have been identified. In the present study, we sought to determine which estrogenic components, at concentrations commensurate with their plasma levels achieved following a single oral dose of 0.625 mg CEE (the dose used in the WHIMS trial) in women, are neuroprotective and whether combinations of those neuroprotective estrogens provide added benefit. Further, we sought, through computer-aided modeling analyses, to investigate the potential correlation of the molecular mechanisms that conferred estrogen neuroprotection with estrogen interactions with the estrogen receptor (ER).Results
Cultured basal forebrain neurons were exposed to either β-amyloid25–35 or excitotoxic glutamate with or without pretreatment with estrogens followed by neuroprotection analyses. Three indicators of neuroprotection that rely on different aspects of neuronal damage and viability, LDH release, intracellular ATP level and MTT formazan formation, were used to assess neuroprotective efficacy. Results of these analyses indicate that the estrogens, 17α-estradiol, 17β-estradiol, equilin, 17α-dihydroequilin, equilinen, 17α-dihydroequilenin, 17β-dihydroequilenin, and Δ8,9-dehydroestrone were each significantly neuroprotective in reducing neuronal plasma membrane damage induced by glutamate excitotoxicity. Of these estrogens, 17β-estradiol and Δ8,9-dehydroestrone were effective in protecting neurons against β-amyloid25–35-induced intracellular ATP decline. Coadministration of two out of three neuroprotective estrogens, 17β-estradiol, equilin and Δ8,9-dehydroestrone, exerted greater neuroprotective efficacy than individual estrogens. Computer-aided analyses to determine structure/function relationships between the estrogenic structures and their neuroprotective activity revealed that the predicted intermolecular interactions of estrogen analogues with ER correlate to their overall neuroprotective efficacy.Conclusion
The present study provides the first documentation of the neuroprotective profile of individual estrogens contained within the complex formulation of CEE at concentrations commensurate with their plasma levels achieved after an oral administration of 0.625 mg CEE in women. Our analyses demonstrate that select estrogens within the complex formulation of CEE contribute to its neuroprotective efficacy. Moreover, our data predict that the magnitude of neuroprotection induced by individual estrogens at relatively low concentrations may be clinically undetectable and ineffective, whereas, a combination of select neuroprotective estrogens could provide an increased and clinically meaningful efficacy. More importantly, these data suggest a strategy for determining neurological efficacy and rational design and development of a composition of estrogen therapy to alleviate climacteric symptoms, promote neurological health, and prevent age-related neurodegeneration, such as AD, in postmenopausal women. 相似文献72.
T. Kasahara H.S. Park D. Shindo H. Yoshikawa T. Sato K. Kondo 《Journal of magnetism and magnetic materials》2006
Domain wall motion in Mn–Zn and Ni–Zn ferrites with applied magnetic fields is investigated by in situ observations with Lorentz microscopy and electron holography. It is found that both Mn–Zn and Ni–Zn ferrites have a mean grain size of approximately 10 μm and several pores with sizes ranging from 0.2 to 1.1 μm. In situ observations by Lorentz microscopy with an applied magnetic field reveals that in Mn–Zn ferrite, the domain walls move easily across the grain boundary, while in Ni–Zn ferrite, the domain walls move along the grain boundary but are pinned at the grain boundary and pores. From in situ observations of Ni–Zn ferrite by electron holography, it is clarified that domain wall pinning at the grain boundary retards a sensitive increase in magnetic flux parallel to the applied field direction, which is considered to result in high hysteresis loss. 相似文献
73.
We have observed the Fano-Kondo antiresonance in a quantum wire with a side-coupled quantum dot. In a weak coupling regime, dips due to the Fano effect appeared. As the coupling strength increased, conductance in the regions between the dips decreased alternately. From the temperature dependence and the response to the magnetic field, we conclude that the conductance reduction is due to the Fano-Kondo antiresonance. At a Kondo valley with the Fano parameter q approximately 0, the phase shift is locked to pi/2 against the gate voltage when the system is close to the unitary limit in agreement with theoretical predictions by Gerland et al. [Phys. Rev. Lett. 84, 3710 (2000)]. 相似文献
74.
We present a fitting method for obtaining a functional form of the refractive index profile of planar microlenses made by ion exchange techniques from total shearing interferometric measurements. Compared to the usual power series expansion fit, this method allows a reduction in the number of coefficients needed to characterize a lens. 相似文献
75.
76.
Combining one stable resonator with a concave mirror and a coupling-hole plane mirror, and another unstable resonator having a concave mirror and a convex mirror, a new hybrid optical resonator type laser has been proposed by overlapping the concave mirror as a common one and fitting the convex mirror exactly to the coupling-hole. Using theABCD law, the so-called g-parameters are first found for beam confinement. Then, based on the eigen-equation, the field distribution on the plano-convex mirror is obtained with the g-parameters above. Knowing this field distribution results in an effective transmittanceG e e. Finally, the ratio of the inner convex to outer plane mirror radii can be determined for an optimum coupling in both the limiting cases of homogeneously and inhomogeneously broadened gain media. Some numerical examples will also be given for a CO2 laser having the proposed hybrid resonator. 相似文献
77.
Makoto Takahashi Masahiro Aoki Hiroshi Sato Tsukuru Ohtoshi Shinji Tsuji 《Optical Review》1996,3(6):484-486
The optimal structure of a laser diode monolithically integrated with a thickness-tapered beam expander waveguide is demonstrated by analyzing the relationship between fiber coupling efficiencies and radiation losses. It is also found that mode conversion loss is lowered in a ridge waveguide structure than in a buried hetero structure under equivalent fiber coupling. A fabricated ridge waveguide device based on this design shows threshold current as low as 16 mA and narrow beam divergences of 13° and 12°. 相似文献
78.
Manabu Ichikawa Yo-ichi Ishikawa Takashi Wakasugi Kohei Kadono 《Journal of luminescence》2012,132(3):784-788
Emission properties were investigated in the infrared region for Ga2S3-GeS2-Sb2S3 glasses doped with Ho3+. We performed Judd–Ofelt analysis and lifetime measurements of the 5I4, 5I5, and 5I6 levels, which are the initial levels of the mid-infrared emissions between 3 to 5 μm of Ho3+. The quantum efficiencies reached approximately 18%, 64%, and ~100% for the 5I4, 5I5, and 5I6, respectively. Population analyses were carried out from the relative intensities of the emissions in the near-infrared region. We investigated the dependences on the Ho3+ ion concentration of the population ratio of the initial levels to the final levels, [initial]/[final], of the mid-infrared emissions. The population ratio of [5I5]/[5I6] decreased with increase of the Ho3+ concentration while those of [5I4]/[5I5] and [5I6]/[5I7] increased. Particularly, the former, [5I4]/[5I5], rapidly increased because of the strong concentration quenching of the 5I5 level through cross relaxation. It was found that the population inversion for the 4.8 μm emission due to the transition, 5I4→5I5, was achieved at high Ho3+ concentration in the present experiments. 相似文献
79.
80.