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We assessed the possibility of changing the route of administration of zoledronic acid to an oral dosage form and its therapeutic efficacy in an estrogen-deficient osteoporosis rat model. To enhance oral bioavailability, we formed an ionic complex by electrostatic conjugation of zoledronic acid with lysine-linked deoxycholic acid (Lys-DOCA, an oral absorption enhancer). After forming the complex, the characteristic crystalline features of pure zoledronic acid disappeared completely in the powder X-ray diffractogram and differential scanning calorimetry thermogram, indicating that zoledronic acid existed in an amorphous form in the complex. In vitro permeabilities of zoledronic acid/Lys-DOCA (1:1) (ZD1) and zoledronic acid/Lys-DOCA (1:2) (ZD2) complex across Caco-2 cell monolayers were 2.47- and 4.74-fold higher than that of zoledronic acid, respectively. Upon intra-jejunal administration to rats, the intestinal absorption of zoledronic acid was increased significantly and the resulting oral bioavailability of the ZD2 complex was determined to be 6.76 +/- 2.59% (0.548 +/- 0.161% for zoledronic acid). Ovariectomized (OVX) rats showed 122% increased bone mineral density versus the OVX control at 12 weeks after treatment with once weekly oral administration of ZD2 complex (16 mu g/kg of zoledronic acid). Furthermore, rats treated with ZD2 complex orally showed significant improvement in the parameters of trabecular microarchitecture and bone strength: 149% higher bone volume fraction (BV/TV), 115% higher trabecular number (Tb.N), and 56% higher mean maximum load (F-max) than in the OVX group. The trabecular microstructure and bone mechanical properties in the oral zoledronic acid group were not significantly changed compared with the OVX control. Thus, the oral ZD2 complex inhibited osteoporosis progression effectively by promoting osteogenesis and trabecular connectivity. The oral ZD2 complex would be expected to improve patient compliance by replacing the conventional injectable form and expand the indications, to include prophylaxis for osteoporosis and bone metastases.

Nuclear level densities and γ-ray strength functions have been extracted for 89,90Y, using the Oslo Method on data sets from the 89Y(p,p')89Y and 89Y(d,p)90Y reactions. The γ-ray strength functions display a low-energy enhancement consistent with previous observations in this mass region (93-98Mo). Shell-model calculations give support that the observed enhancement is due to strong, low-energy M1 transitions at high excitation energies. The data were further used as input for calculations of the 88 Sr(p,γ)89Y, 88Y(n,γ)89Y, and 89Y(n,γ)90Y cross sections with the TALYS reaction code. Comparison with cross-section data, when available, shows a satisfying agreement, as well as with values from the BRUSLIB library.

The regulation of angiogenesis is an interesting area to consider for novel therapeutic approaches to rheumatoid arthritis (RA). Chemically modified heparins have been developed as possible candidates for angiogenesis inhibitor; however, they have a major clinical drawback in exhibiting poor oral bioavailability. Here, orally absorbable O-desulfated low molecular weight heparin (ODS-LMWH) derivatives were newly synthesized by conjugating 2-O-or 6-O-desulfated LMWH with deoxycholic acid (DOCA) or bisDOCA (a dimer of DOCA), and their physicochemical properties, antiangiogenic potency and pharmacokinetic profiles were assessed. After selecting the best candidate among those derivatives, its therapeutic efficacy on arthritis was investigated in a murine collagen antibody-induced arthritis (CAIA) model. ODS-LMWH derivatives significantly inhibited the capillary-like tube formation of humanumbilical vein endothelial cells (HUVECs) and basic fibroblast growth factor (bFGF)-induced angiogenesis in the Matrigel plug assay. Among all the compounds, 6ODS-LHbD showed the highest oral bioavailability in rats (19.3%). In the CAIA mouse model, 6ODS-LHbD (10 mg/kg, p.o., S. I. D.) significantly inhibited neovascularization in the joint, the increase of hind-pawthickness, and the structural damage in the bone. Therefore, 6ODS-LHbD would be a promising candidate for an orally active drug for the treatment of RA.

We have analyzed the first 3.75 years of data from the Taiwanese American Occultation Survey (TAOS). TAOS monitors bright stars to search for occultations by Kuiper Belt objects (KBOs). This data set comprises 5 × 10^5 star hours of multi-telescope photometric data taken at 4 or 5 Hz. No events consistent with KBO occultations were found in this data set. We compute the number of events expected for the Kuiper Belt formation and evolution models of Pan & Sari, Kenyon & Bromley, Benavidez & Campo Bagatin, and Fraser. A comparison with the upper limits we derive from our data constrains the parameter space of these models. This is the first detailed comparison of models of the KBO size distribution with data from an occultation survey. Our results suggest that the KBO population is composed of objects with low internal strength and that planetary migration played a role in the shaping of the size distribution.

We use the far-UV (FUV) and near-UV (NUV) images of M83 obtained by GALEX to compute the radial profile of the UV spectral slope in the star forming disk. We briefly present a model of its chemical evolution which allows us to obtain realistic intrinsic properties of the stellar populations. Using corollary data, we also compute the profiles of H-alpha/H-beta and of the total IR (TIR) to FUV ratio. Both data and model are used to estimate and compare the extinction gradients at the FUV wavelength obtained from these various indicators. We discuss the implications for the determination of the star formation rate., Comment: This paper will be published as part of the Galaxy Evolution Explorer (GALEX) Astrophysical Journal Letters Special Issue. Links to the full set of papers will be available at http://www.galex.caltech.edu/PUBLICATIONS/ after November 22, 2004. A high resolution version of figure 1 is available at http://www.ociw.edu/~boissier/M83/fig1.ps

The GALEX (Galaxy Evolution Explorer) Nearby Galaxies Survey is providing deep far-UV and near-UV imaging for a representative sample of galaxies in the local universe. We present early results for M51 and M101, from GALEX UV imaging and SDSS optical data in five bands. The multi-band photometry of compact stellar complexes in M101 is compared to population synthesis models, to derive ages, reddening, reddening-corrected luminosities and current/initial masses. The GALEX UV photometry provides a complete census of young compact complexes on a approximately 160pc scale. A galactocentric gradient of the far-UV - near-UV color indicates younger stellar populations towards the outer parts of the galaxy disks, the effect being more pronounced in M101 than in M51., Comment: This paper will be published as part of the Galaxy Evolution Explorer (GALEX) Astrophysical Journal Letters Special Issue. Full paper available from http://dolomiti.pha.jhu.edu . Links to full set of papers will be available at http://www.galex.caltech.edu/PUBLICATIONS/ after November 22, 2004

The ELAIS S1 field was observed by GALEX in both its Wide Spectroscopic and Deep Imaging Survey modes. This field was previously observed by the Infrared Space Observatory and we made use of the catalogue of multi-wavelength data published by the ELAIS consortium to select galaxies common to the two samples. Among the 959 objects with GALEX spectroscopy, 88 are present in the ELAIS catalog and 19 are galaxies with an optical spectroscopic redshift. The distribution of redshifts covers the range $0, Comment: This paper has been published as part of the GALEX ApJL Special Issue (ApJ 619, L63)

M32, the compact elliptical-galaxy companion to the Andromeda spiral galaxy has been imaged by the Galaxy Evolution Explorer (GALEX) in two ultraviolet bands, centered at ~1500 (FUV) and 2300 Angstroms (NUV). The imaging data have been carefully decomposed so as to properly account for the complicated background contamination from the disk of M31. We have derived the surface brightness and color profiles finding a slightly positive color gradient of Delta(FUV-B)/Delta log(r)=+0.15+/-0.03 within one effective radius. Earlier data from the Ultraviolet Imaging Telescope suggested that M32 had an extremely large (negative) FUV-optical color gradient (Delta(FUV-B)/Delta log(r), Comment: 5 pages, 3 figures. This paper will be published as part of the Galaxy Evolution Explorer (GALEX) Astrophysical Journal Letters Special Issue. Links to the full set of papers will be available at http://www.galex.caltech.edu/PUBLICATIONS/ after November 22, 2004