Narrow-Band Red-Emitting Phosphors with High Color Purity, Trifling Thermal and Concentration Quenching for Hybrid White LEDs and Li3Y3BaSr(MoO4)8:Sm3+, Eu3+-Based Deep-Red LEDs for Plant Growth Applications.

Trivalent europium-based monochromatic red light-emitting phosphors are an essential component to realize high-performance smart lighting devices; however, the concentration and thermal quenching restrict their usage. Here, we report a series of efficient Eu3+-substituted Li3Y3BaSr(MoO4)8 red-emitting phosphors based on a stratified scheelite structure with negligible concentration and thermal quenching. All of the host and phosphor compositions crystallize in monoclinic crystal structure (space group C2/c). All of the phosphor compositions produce narrow-band red emission (FWHM ∼6 nm), which is highly apparent to the human eyes, and lead to exceptional chromatic saturation of the red spectral window. Concurrently, detailed investigations were carried out to comprehend the concentration and thermal quenching mechanism. Absolute quantum yields as high as 88.5% were obtained for Li3Y0.3Eu2.7BaSr(MoO4)8 phosphor with virtuous thermal stability (at 400 K, retaining 87% of its emission intensity). The light-emitting diodes were constructed by coupling Li3BaSrY0.3Eu2.7(MoO4)8 red phosphor with a near-UV LED chip (395 nm) operated at 20 mA forward bias, and the hybrid white LED (an organic yellow dye + red Li3Y3BaSr(MoO4)8:Eu3+ phosphor integrated with an NUV LED chip) showed a low CCT (6645 K), high CRI (83) values, and CIE values of x = 0.303; y = 0.368, which indicated that the synthesized phosphors can be a suitable red component for white LEDs. In addition, we have systematically investigated the Sm3+ and Sm3+, Eu3+ activation in Li3Y3BaSr(MoO4)8 to display the latent use of the system in plant growth applications and establish that the phosphor exhibits orange red emission with an intense deep-red emission (645 nm (4G5/2 → 6H9/2)). The phytochrome (Pr) absorption spectrum well matched the fabricated deep-red LED (by integrating a NUV LED + Li3Y3BaSr(MoO4)8:Sm3+ and Eu3+ phosphor) spectral lines.

Applicability of Reddish-Orange Light Emitting Samarium (III) Complexes for Biomedical and Multifunctional Optoelectronic Devices.

Six crimson samarium (III) complexes based on ß-ketone carboxylic acid and ancillary ligands were synthesized by adopting the grinding technique. All synthesized complexes were investigated via elemental analysis, infrared, UV-Vis, NMR, TG/DTG and photoluminescence studies. Optical properties of these photostimulated samarium (III) complexes exhibit reddish-orange luminescence due to 4G5/2 → 6H7/2 electronic transition at 606 nm of samarium (III) ions. Further, energy bandgap, color purity, CIE color coordinates, CCT and quantum yield of all complexes were determined accurately. Replacement of water molecules by ancillary ligands enriched these complexes (S2-S6) with decay time, quantum yield, luminescence, energy bandgap and biological properties than parent complex (S1). Interestingly, these efficient properties of complexes may find their applications in optoelectronics and lighting systems. In addition to these, the antioxidant and antimicrobial assays were also investigated to explore the applications in biological assays.

Samarium enriches antitumor activity of ZnO nanoparticles via downregulation of CXCR4 receptor and cytochrome P450.

Cancer is the leading cause of death and exhausts human and economic resources for treatment and protection. Zinc oxide nanoparticles play an effective role in tumor treatment but with some cautions, such as overexpression of cytochrome P450, hepatic overload, and the mammalian target of rapamycin pathway resistance. Although lanthanides have antitumor activity, their use is limited. Therefore, the current study aims to improve the effectiveness of zinc oxide nanoparticle via doping with lanthanides, such as samarium. In vitro study revealed that samarium doped with zinc oxide showed more antitumor activity than the other lanthanides, and the antitumor activity depends on the concentration of samarium in the nanocomposite. The in vivo experiment on mice bearing Ehrlich solid tumor revealed that intramuscular injection of samarium/zinc oxide downregulates the expressions of CXCR4 and PI3K/Akt/mammalian target of rapamycin pathway in respect to Ehrlich solid tumor group. Regarding the apoptotic biomarkers, samarium/zinc oxide upregulates the apoptotic biomarker; Bax accompanied with the mitotic catastrophe which was indicated by cell cycle arrest in G2 phase. Moreover, samarium:zinc oxide nanoparticles exhibited minimum toxicity which was indicated by suppressed activities of cytochrome P450 and hepatic enzymes, including alanine transaminase and aspartate transaminase. In addition, the histopathological finding, as well as immunophenotyping results, appreciated the biochemical finding. Therefore, samarium:zinc oxide might be offered a new approach to improve the effectiveness of zinc oxide nanoparticles along with lower toxic effect. Also, samarium:zinc oxide nanoparticles can be a candidate as a new antitumor compound to detect its mode of action.

Efficacy and safety of 153Sm-EDTMP as treatment of painful bone metastasis: a large single-center study.

PURPOSE: The purpose of this study is to assess the efficacy of 153Sm-EDTMP (Quadramet®) in a clinical setting. METHODS: We have conducted a retrospective study of all consecutive patients (pts) treated with 153Sm-EDTMP for painful bone metastases. At each visit (before and after treatment), four parameters were collected: (i) pain assessment according to the 10-step visual analogue scale (VAS), (ii) sleep disturbance related to pain, (iii) dose of analgesic medication, and (iv) answer to the following closed question "Do you think you obtained a benefit from treatment?" Success of treatment was defined by the combination of these four parameters. RESULTS: Three hundred seventy consecutive 153Sm-EDTMP treatments for painful bone metastases were given. Patients had the following primary tumors: breast carcinoma (153), prostate carcinoma (155), lung carcinoma (27), or other cancers (35). Fifty-eight percent of the patients had received previous external osseous radiotherapy. Ninety-seven percent of the patients were treated with concomitant analgesics and 61% were treated with diphosphonates. A clinical benefit was described in 55.0% of cases at D30. Treatment was more effective in cases of breast and prostate cancers compared with other types of primary cancers. Patients described a benefit at D30 in 62, 58, 6, and 38% of cases of breast, prostate, lung, and other cancers. The subjective efficacy was accompanied by a decrease in analgesic intake in 35.0% of cases. CONCLUSION: 153Sm-EDTMP therapy is an effective supportive treatment in patients who suffer from bone metastases, especially in patients with breast or prostate cancer.

Anti-amoebic activity of acyclic and cyclic-samarium complexes on Acanthamoeba.

This work investigated the anti-amoebic activity of two samarium (Sm) complexes, the acyclic complex [bis(picrato)(pentaethylene glycol)samarium(III)] picrate-referred to as [Sm(Pic)2(EO5)](Pic)-and the cyclic complex [bis(picrato)(18-crown-6)samarium(III)] picrate-referred to as [Sm(Pic)2(18C6)](Pic). Both Sm complexes caused morphological transformation of the protozoa Acanthamoeba from its native trophozoite form carrying a spine-like structure called acanthopodia, to round-shaped cells with loss of the acanthopodia structure, a trademark response to environmental stress. Further investigation, however, revealed that the two forms of the Sm complexes exerted unique cytotoxicity characteristics. Firstly, the IC50 of the acyclic complex (0.7 µg/mL) was ~ 10-fold lower than IC50 of the cyclic Sm complex (6.5 µg/mL). Secondly, treatment of the Acanthamoeba with the acyclic complex caused apoptosis of the treated cells, while the treatment with the cyclic complex caused necrosis evident by the leakage of the cell membrane. Both treatments induced DNA damage in Acanthamoeba. Finally, a molecular docking simulation revealed the potential capability of the acyclic complex to form hydrogen bonds with profilin-a membrane protein present in eukaryotes, including Acanthamoeba, that plays important roles in the formation and degradation of actin cytoskeleton. Not found for the cyclic complex, such potential interactions could be the underlying reason, at least in part, for the much higher cytotoxicity of the acyclic complex and also possibly, for the observed differences in the cytotoxicity traits. Nonetheless, with IC50 values of < 10 µg/mL, both the acyclic and cyclic Sm complexes feature a promising potential as cytotoxic agents to fight amoebic infections.

Effects of rare earth element samarium doped zinc oxide nanoparticles on Mytilus galloprovincialis (Lamarck, 1819): Filtration rates and histopathology.

BACKGROUND: Doping was reported to improve the photo catalytic performance, antioxidant, antibacterial and other biological properties of nanoparticles. While, improving the nanoparticle properties, doping could change toxicity profile to living organism. Hence, the aim of this work was to assess the effects of samarium doped zinc oxide nanoparticles (Sm doped ZnO NPs) on the edible mussel Mytilus galloprovincialis. METHODS: Sm doped ZnO nanoparticles were characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR) techniques. 156 mussels were exposed during 7 days to a low, intermediate and high concentration of Sm doped ZnO NPs (0.5, 1 and 1.5 mg/L, respectively). The filtration rates were assessed after 1 and 2 h. Histopathological alterations were determined in gills, digestive glands and gonads using a quantitative analysis. RESULTS: The filtration rates decreased in all individuals exposed to Sm doped ZnO NPs, a significant decrease was noted with the low and intermediate concentration (0.5 and 1 mg/L) of Sm doped ZnO NPs after 1 and 2 h, respectively. The histopathological index (Ih) estimated for gills, digestive glands and gonads showed differences depending on the organ and the nanoparticle concentration. The highest Ih were reported for digestive glands and female gonads exposed to the intermediate concentration (1 mg/L) of Sm doped ZnO NPs. As for gills and male gonads, the highest Ih were noted with the high concentration (1.5 mg/L) of Sm doped ZnO NPs. CONCLUSION: Results from this study revealed the toxicity of Sm doped ZnO NPs in Mytilus galloprovincialis gills, digestive glands and gonads. The toxicity induced by this nanoparticle varies depending on the organ and the concentration.

Cerium- and samarium-nitrate interaction and accumulation on human dentin.

OBJECTIVE: To investigate the accumulation of cerium-nitrate and samarium-nitrate on dentin without or with smear-layer and to test their antibacterial activity. DESIGN: 24 dentin-enamel slices were cut from 24 extracted molars. 12 slices underwent smear-layer creation (320 grit, 200 g, 5 s), the other 12 smear-layer removal (20 % EDTA, 300 s). Slices were halved to 48 semilunar-shaped specimens. One specimen per tooth was treated with either Ce(NO3)3 (50 wt% aqueous solution; pH = 1.29; n = 6) or Sm(NO3)3 (50 wt% aqueous solution; pH = 1.88; n = 6). The other specimen served as control (A. demin). After water rinsing, elemental composition (Ce, Sm, Ca, P, O, N, Na, Mg, C) was measured (EDX; EDAX Octane-Elect, APEX v2.5, low-vacuum) in dentin. Atomic percent (At%), Ca/P- and Ca/N-ratios were calculated and analyzed non-parametrically (α = 0.05, error rates method). Additionally, antibacterial activity (2 min exposure) of Ce(NO3)3 and Sm(NO3)3 against Streptococcus mutans, Actinomyces naeslundii, Schaalia odontolytica, and Enterococcus faecalis was determined (colony forming units) after anaerobic incubation at 37 °C for 24 h (control: 0.2 % CHX). RESULTS: At% (median) of Ce and Sm were as follows: Ce(NO3)3 3.4 and 0.9 At%Ce with and without smear-layer, respectively; Sm(NO3)3 2.4 and 1.3 At%Sm with and without smear-layer, respectively. Ce(NO3)3 and Sm(NO3)3-application significantly decreased Ca/P-ratios (1.22 - 1.45; p ≤ 0.02) compared to controls (1.47 - 1.63). With smear-layer, significantly higher Ca/N-ratios (5.1 - 29.3) could be detected across all groups (p ≤ 0.004) compared to specimens without smear-layer (0.37 - 0.48). Ce(NO3)3 and Sm(NO3)3 showed reduction rates of up to ≥ 5 log10 steps for S. mutans, A. naeslundii, and S. odontolytica. CONCLUSIONS: Cerium and samarium nitrate showed accumulation on dentin and certain antibacterial activity and could therefore be identified as potential compounds to treat and prevent dentin and root caries and dentin hypersensitivity.

Radioactive synovectomy with (90) yttrium and (153) samarium hydroxyapatite in haemophilic joints: preliminary study on radiation safety.

Most countries still do not achieve 1 IU of factor VIII/capita sufficient for survival. Although primary prophylaxis prevents synovitis, is not universally used. Chronic synovitis is treated with arthroscopy at expense of considerable amount of coagulation factors, and specialized surgeons. Radioactive synovectomy (RS) is a minimally invasive and cost effective alternative to arthroscopy, often considered first the option for persistent synovitis. Even without established causation with cancer, RS is avoided by some, due to this concern. We aim contributing to the understanding of RS safety regarding malignancy, presenting a large number of treated patients, and a single case of cancer. Three centres in Brazil applied RS with (90) Yttrium Citrate, (90) Yttrium hydroxyapatite or (153) Samarium hydroxyapatite in haemophilic joints and performed a survey addressing cancer in these patients. Four hundred and eighty eight patients (ages 3-51) received 1-3 RS (total 842) and follow-up was 6 months to 9 years. One patient aged 14 years presented Ewing sarcoma, 11 months after RS. The tumour was treated successfully with surgery and chemotherapy. Causality of cancer by RS is improbable in this case. Accordingly, latency here is far below minimum 5-10 years for radio-induction of solid tumours. Moreover, ES is not a typically radio-induced tumour, even at high doses. In agreement with others, though recognizing limitations, this study suggests RS is safe regarding cancer induction. Synovitis is a known burden for patients. The decision of making reasonable usage of RS should be outweighed with the risks of leaving synovitis untreated.

Cerium and samarium blocked antioxidant enzymes in wheat plants.

This work was conducted to study positive and negative impacts of cerium (Ce) and samarium (Sm) on two cultivars (Arta and Baharan) in wheat plant. Symbols of stress such as proline, malondialdehyde (MDA) and antioxidant enzymes, which may be complicated in the suppression responses of plants, were also studied. Wheat plants were exposed to 0, 2500, 5000, 7500, 10,000 and 15,000 µM of Ce and Sm for 7 days. The growth enhanced in plants treated with lesser Ce and Sm concentration (2500 µM) and declined in plants treated with upper concentrations as compared to untreated plants. The treatment with 2500 µM of Ce and Sm increased dry weigh in Arta by 68.42 and 20% and in Baharan by 32.14% and 27.3%. Thus, Ce and Sm had hormesis effect on growth in wheat plants. According to plant's growth parameter patterns, Arta cultivar had more sensitive to Sm than to Ce, whereas Baharan cultivar had sensitive to Ce than to Sm. Our results indicated impact of Ce and Sm on proline accumulation depended on the dosage of Ce and Sm. It was observed that Ce and Sm accumulated in wheat plants at higher exposure doses. Increment of MDA content by Ce and Sm treatments showed that these metals caused oxidative stress in wheat plants. Ce and Sm blocked enzymatic antioxidant system (superoxide dismutases, peroxidase and polyphenol peroxidase) in wheat. In wheat plants treated with lower Ce and Sm concentrations higher amounts of non-enzymatic antioxidant metabolites were detected. Thus, we showed the potential negative impact of unsuitable utilization of REEs in plants and suggested growth and interruption in physiological and biochemical mechanisms as a possible factor to recognize the underlying toxicological processes.

Effects of metals on skin permeability barrier recovery.

We previously demonstrated that the electrical state of the skin surface influences epidermal permeability barrier homeostasis. At the interface between different materials, electrons are localized heterogeneously and induce electrical potential. In the present study, we evaluated the effects of metals on the barrier recovery. When we put pure gold plate on skin immediately after tape stripping, the barrier recovery rate was faster than the control. The acceleration of barrier recovery was blocked when the plate was earthed (grounded). When a plastic membrane was sandwiched between the plate and the skin, the recovery was delayed in comparison with the control. We then used a germanium diode to regulate the current flow between the plate and the earth. When the current was blocked, the barrier recovery was accelerated, but when the current was not blocked, the recovery was not accelerated. These results suggest that localization of electron might affect for the barrier recovery rate. The level of interfacial electric potential would be different due to the electrochemical property of metal. Thus, we next evaluated the effects of other metals. With samarium, zirconium, iridium and silver, the barrier recovery rate was faster than in the case of gold, while a platinum plate induced slower recovery than in the case of gold. There was a significant correlation between work function of each metal and barrier recovery rate. These results suggest that electron donation from outside accelerated the skin barrier recovery.

Evaluation of a method for activity estimation in Sm-153 EDTMP imaging.

Absolute activity evaluation is fundamental for internal radionuclide dosimetry when patient-specific therapy optimization is wanted. Often, quantification is attempted with 3D SPECT image based (IB) methods, but the true concentration values can be underestimated due to the partial volume effect (PVE). This is especially true when small diffuse lesions are present. In this paper, we describe a 3D region of interest (ROI) based quantification method (LS-ROI), which estimates the ROI concentration values directly from the projection data acquired in the tomographic scan once ROIs have been segmented on a CT and/or a SPECT image. The method, which has inherent PVE correction capabilities, was applied both on simulated and on real phantom data. Simulations reflected the case of a patient with bone metastases treated with 153Sm-EDTMP: Both the activity in the metastases and the total retention in the skeleton were evaluated. Thirty noisy data sets were produced in order to evaluate the accuracy and precision of the method. The effect of region segmentation errors on estimated concentrations was thoroughly investigated. Real data were acquired on a NEMA phantom, where a cylindrical central region (283 cm3) simulated the bone and two spheres (10.3 and 25.5 cm3) simulated the metastases. The results obtained with the LS-ROI method were compared with those of a conventional 3D IB method and those of a quantitative conjugate view approach derived from LS-ROI and applied to the anterior and posterior views acquired in the tomographic scan (LS-ROI anterior-posterior: LS-ROI-AP). Simulations showed that when the geometry of regions is known, the LS-ROI method recovered the simulated concentration values within 20%, while the IB method underestimated the concentration in high activity small lesions by as much as 49%. Segmentation errors, up to 44% of the true region volume, produced a higher variation in LS-ROI estimates than in IB ones; however, the overall bias of the LS-ROI estimates (< or = 25%) remained lower than that of IB estimates. In the case of the evaluation of the total retention in the skeleton, the LS-ROI method recovered the simulated value within 2%, while IB underestimated it up to 13%. In all the cases, the LS-ROI-AP method showed an accuracy comparable with that of the LS-ROI one, and a worse precision just because of the lower number of counts used in the analysis. However, a worsening of LS-ROI-AP performances was demonstrated in the case of strong overlap of regions: In this case, a bias of up to 40% was observed. The results obtained on real phantom data confirmed the simulation results: The IB method underestimated activity up to 47% in the smallest sphere, while the bias was reduced to 13% with LS-ROI and LS-ROI-AP estimates. The good quantification capabilities of the LS-ROI method can be useful for absolute activity quantification in the case of small active diffused lesions and constitute the basis for the development of an accurate patient-specific planning strategy in internal radionuclide treatments, provided there is a reliable segmentation of lesions.

The use of chelated radionuclide (samarium-153-ethylenediaminetetramethylenephosphonate) to modulate phenotype of tumor cells and enhance T cell-mediated killing.

PURPOSE: Exposing human tumor cells to sublethal doses of external beam radiation up-regulates expression of tumor antigen and accessory molecules, rendering tumor cells more susceptible to killing by antigen-specific CTLs. This study explored the possibility that exposure to palliative doses of a radiopharmaceutical agent could alter the phenotype of tumor cells to render them more susceptible to T cell-mediated killing. EXPERIMENTAL DESIGN: Here, 10 human tumor cell lines (4 prostate, 2 breast, and 4 lung) were exposed to increasing doses of the radiopharmaceutical samarium-153-ethylenediaminetetramethylenephosphonate ((153)Sm-EDTMP) used in cancer patients to treat pain due to bone metastasis. Fluorescence-activated cell sorting analysis and quantitative real-time PCR analysis for expression of five surface molecules and several tumor-associated antigens involved in prostate cancer were done. LNCaP human prostate cancer cells were exposed to (153)Sm-EDTMP and incubated with tumor-associated antigen-specific CTL in a CTL killing assay to determine whether exposure to (153)Sm-EDTMP rendered LNCaP cells more susceptible to T cell-mediated killing. RESULTS: Tumor cells up-regulated the surface molecules Fas (100% of cell lines up-regulated Fas), carcinoembryonic antigen (90%), mucin-1 (60%), MHC class I (50%), and intercellular adhesion molecule-1 (40%) in response to (153)Sm-EDTMP. Quantitative real-time PCR analysis revealed additional up-regulated tumor antigens. Exposure to (153)Sm-EDTMP rendered LNCaP cells more susceptible to killing by CTLs specific for prostate-specific antigen, carcinoembryonic antigen, and mucin-1. CONCLUSIONS: Doses of (153)Sm-EDTMP equivalent to palliative doses delivered to bone alter the phenotype of tumor cells, suggesting that (153)Sm-EDTMP may work synergistically with immunotherapy to increase the susceptibility of tumor cells to CTL killing.

Self-Assembled Metal-Phenolic Nanoparticles for Enhanced Synergistic Combination Therapy against Colon Cancer.

Engineering functional nanomaterials to have both high therapeutic efficacy and minimal side-effects has become a promising strategy for next-generation cancer treatments. Herein, an adenosine triphosphate (ATP) depletion and reactive oxygen species-enhanced combination chemotherapy platform is introduced whereby therapeutic samarium (Sm3+ ) ions and (-)-epicatechin (EC) are integrated via a metal-phenolic network (SmIII -EC). The independent pathway between Sm3+ and EC can achieve a synergistic therapeutic effect through the mitochondrial dysfunction process. SmIII -EC nanoparticles cause a significant reduction of viability of C26 murine colon carcinoma cells while with lower systemic toxic effects on normal cell lines. SmIII -EC nanoparticles are used to directly compare with a clinic anticancer drug 5-fluorouracil. SmIII -EC nanoparticles not only decrease the tumor volume but also do not affect the body weight of mice and normal organs, showing significant advantages over clinic counterpart. These facts suggest that SmIII -EC nanoparticles represent a clinically promising candidate for colon cancer treatment with a targeted therapeutic effect and minimum side toxicity.

Lithium ions (Li+) and nanohydroxyapatite (nHAp) doped with Li+ enhance expression of late osteogenic markers in adipose-derived stem cells. Potential theranostic application of nHAp doped with Li+ and co-doped with europium (III) and samarium (III) ions.

Lithium (Li+) ion due to its excellent bioactivity is one of the most well-studied element in bone-tissue engineering. In this study, we fabricated nanohydroxyapatite (nHAp) doped with Li+ ions (5 mol% Li+:nHAp) and co-doped with lanthanide ions. We investigated the effects of nHAp, 5 mol% Li+:nHAp or Li+ alone, on osteogenic differentiation of human Adipose Tissue-derived Stem Cells (hASCs), their proliferation, mitochondrial dynamics and apoptosis. Moreover, we monitored cell proliferation after treatment with samarium (III) (Sm3+) and europium (III) (Eu3+) ions co-doped 5 mol% Li+:nHAp as well as their luminescent property. The hASCs treated with 5 mol% Li+:nHAp and Li+ ions proliferated more rapidly and differentiated effectively than control cells without undergoing apoptosis. Both, 5 mol% Li+:nHAp and Li+ ions improved osteogenic differentiation of hASCs. Moreover they decreased expression of glycogen synthase kinase 3ß (GSK3ß) while increased ß-catenin mRNA level. In addition, Li+, nHAp and 5 mol% Li+:nHAp improved mitochondrial dynamics and enhanced expression of neural differentiation marker genes. Collectively, the study indicates on pro-osteogenic and anti-apoptotic properties of nHAp doped with Li+ and Li+ alone. Moreover, unique properties of 5 mol% Li+:nHAp and 5 mol% Li+:nHAp co-doped with rare earth ions, such as Sm3+ and Eu3+ have shed a promising light on their potential application in theranostics.

Fabrication of Gd/Eu-codoped SmPO4 nanorods for dual-modal magnetic resonance and bio-optical imaging.

Ln-based complexes can be used as T1-enhanced contrast agents of magnetic resonance (MR) imaging in clinical field. Herein, we present a facile and feasible biomineralization process to fabricate Gd/Eu-codoped SmPO4 nanorods (NRs) with silk fibroin (SF) peptides (codoped SF-NRs) as T1-enhanced contrast agents, which possess paramagnetic property, photoluminescence (PL), better cyto-/tissue-compatibility and longer half-life in blood due to SF coating on their surface. Their bio-distributions in TB-N mice via tail-vein injection indicated that, although SF-NRs could be safely cleared away through renal and fecal excretion, SF-NRs easily permeated and aggregated in tumors. The results of in vitro MR imaging demonstrate that the longitudinal relaxivity r1 value of codoped SF-NRs (0.31 Sm-Gd mM(-1) s(-1)) is not only significantly higher than those of Gd-doped and Eu-doped SmPO4 SF-NRs, but also higher than those of codoped pure NRs. The tests of in vivo T1 weighted MR imaging via intro-tumor injection and tail-vein injection confirm that, compared to the pure NRs, the codoped SF-NRs exhibited higher positive signal-enhancement ability. Furthermore, the better luminescence imaging of living cells under the fluorescence microscope (94% stronger than that of the NRs without SF). A formation mechanism of codoped SF-NRs is proposed, to explain the synergistic effect of Gd/Eu codoping and SF coating on their enhanced bio-compatibility, half-life in blood, T1-weighted MR imaging and PL imaging.

Synthesis of complex nucleoside antibiotics.

Herbicidin B and fully prtected tunicaminyluracil, which were undecose nucleoside antibiotics, were synthesized using a samarium diiodide (SmI2) mediated aldol reaction with the use of alpha-phenylthioketone as an enolate. The characteristics of the SmI2-mediated aldol reaction are that the enolate can be regioselectively generated and the aldol reaction proceeds under near neutral condition. This reaction is proved to be a powerful reaction for the synthesis of complex nucleoside antibiotics. The synthesis of caprazol, the core structure of caprazamycins, was conducted by the strategy including beta-selective ribosylation without using a neighboring group participation and the construction of a diazepanone by a modified reductive amination. Our synthetic route would provide a range of key analogues with partial structures to define the pharmacophore, which can be a lead for the development of more effective anti-bacterial agents.

Synthesis, spectroscopic, thermal and antimicrobial studies of neodymium(III) and samarium(III) complexes derived from tetradentate ligands containing N and S donor atoms.

Trivalent lanthanide complexes of the type [Ln(L)Cl(H2O)2] (where Ln=Nd(III) or Sm(III) and LH2=Schiff bases derived by the condensation of 3-(phenyl/substitutedphenyl)-4-amino-5-mercapto-1,2,4-triazole with diacetyl/benzil) have been synthesized by the reactions of anhydrous lanthanide(III) chloride with Schiff bases in methanol. The structures of the complexes have been proposed on the basis of elemental analysis, electrical conductance, magnetic moment, spectroscopic measurements (IR, 1H, 13C NMR and UV-vis spectra) and X-ray diffraction studies. The spectral data reveal that the Schiff base ligands behave as dibasic tetradentate chelating agents having coordination sites at two thiol sulfur atoms and two azomethine nitrogen atoms. The presence of coordinated water in metal complexes was confirmed by thermal and IR data of the complexes. All the Schiff bases and their metal complexes have also been screened for their antibacterial activity against Bacillus subtilis, Staphylococcus aureus and antifungal activities against Aspergillus niger, Curvularia pallescens and Colletotrichum capsici.

Calcium and pancreatic beta-cell function. IX. Demonstration of lanthanide-induced inhibition of insulin secretion independent of modifications in transmembrane Ca2+ fluxes.

beta-Cell-rich pancreatic islets were microdissected from noninbred ob/ob-mice and used to examine the mode of action of trivalent lanthanide ions on insulin secretion. La3+, Sm3+, and Tm3+ were equally effective inhibitors of basal and glucose-stimulated insulin release. As indicated by perifusion experiments with Tm3+, the inhibitory action was prompt, sustained, and readily reversible. Despite the similarities among the lanthanides in inhibiting insulin secretion, these cations differed considerably in their ability to impair transmembrane 45Ca fluxes. Using 10 different members of the lanthanide series, it was possible to demonstrate that their effectiveness to inhibit 45Ca uptake increased with ionic radius. La3+ markedly inhibited intracellular uptake and superficial binding of 45Ca at both 3 and 20 mM glucose. However, Tm3+ failed to affect intracellular 45Ca uptake and only reduced superficial binding of 45Ca at 3 mM glucose. In efflux experiments, Tm3+ did not affect basal or glucose-stimulated 45Ca washout from islets perifused with a medium containing 1.28 mM Ca2+. In a Ca2+-deficient medium, Tm3+ caused a slight transient increase, followed by reduction of 45Ca washout. However, when glucose was omitted, there was a prompt increase in the washout of radioactivity in the presence of Tm3+. Accordingly, the potent inhibitory action of Tm3+ on insulin secretion is not matched by changes in transmembrane Ca2+ fluxes. Since the lanthanides do not penetrate intracellularly, we propose the existence of cationic binding sites in the beta-cell plasma membrane with direct inhibitory effects on insulin secretion.

Rare earth elements as nonabsorbable fecal markers in studies of iron absorption.

The use of rare earth elements as nonabsorbable fecal markers for studies of iron absorption from sources labeled extrinsically with stable isotopes was evaluated. On 3 successive days 13 healthy fasting adults were given different stable isotopes of iron with samarium, ytterbium, or dysprosium. On day 1, three meals were given with 57Fe (1 mg per meal) plus samarium (0.33 mg per meal); on day 2, identical meals (taken with a calcium supplement to reduce iron bioavailability) were given with equivalent amounts of 58Fe-labeled iron and ytterbium; on day 3, a well-absorbed reference dose of 54Fe (3 mg) was given with 1 mg Dy. A complete fecal collection was carried out for 5-9 d and each stool was analyzed for rare earth elements by inductively coupled plasma-mass spectrometry and iron isotopes by thermal ionization quadrupole mass spectrometry. Mean recovery of rare earth elements was 101%, indicating that they are totally unabsorbed. The excretory pattern of the iron isotopes and the rare earth elements was very similar; the correlation coefficients between samarium and 57Fe, ytterbium and 58Fe, and dysprosium and 54Fe were 0.992, 0.989, and 0.988, respectively (P < 0.001). Iron absorption was calculated as the difference between isotope dose and fecal excretion. Mean (+/-SEM) iron absorption was 16.7 +/- 2.4%, 4.3 +/- 1.6%, and 40.3 +/- 3.1% on days 1-3, respectively. Predicted values estimated from the first 4 d of pooled feces, using the rare earth element recovery data to produce corrected figures for unabsorbed isotope, were in close agreement: 19.1 +/- 2.1%, 4.6 +/- 1.7%, and 40.8 +/- 3.1%, respectively (P < 0.001). With the diet of medium iron bioavailability and with the highly bioavailable reference dose it was possible to predict iron absorption accurately from only one or two stools, provided that they were sufficiently enriched with isotope and a rare earth element.

Lanthanides inhibit the human noradrenaline, 5-hydroxytryptamine and dopamine transporters.

Transporters for the monoamine neurotransmitters, including noradrenaline, 5-hydroxytryptamine [5-HT] and dopamine, have twelve transmembrane spanning regions and cotransport Na+ and Cl- ions. Another family of Na(+)-dependent transporters is that containing the Na+/glucose and Na+/proline cotransporters that are found in the epithelial cells of renal and intestinal brush border membranes. It has been shown that various trivalent lanthanides can substitute for Na+ for transport of glucose and proline. The aim of this study was to determine the effects of lanthanides on the activities of the human noradrenaline, 5-HT and dopamine transporters. Cultured cells were incubated for 2 min with 10 nM 3H-noradrenaline (SK-N-SH-SY5Y human neuroblastoma cells), 3H-5-HT (JAR human placental choriocarcinoma cells) or 3H-dopamine (COS-7 cells transfected with the cDNA of the human dopamine transporter). Specific amine uptake was determined as the difference between accumulation of the amine in the cells in the absence and presence of a corresponding uptake inhibitor. Under both isotonic (150 mM NaCl or LiCl or 90 mM lanthanide salt) and hypertonic (150 mM NaCl +100 mM LiCl, 250 mM LiCl or 150 mM lanthanide salt) conditions, replacement of Na+ by Li+, La3+, Eu3+ or Sm3+ abolished the specific uptake of noradrenaline in SK-N-SH-SY5Y cells and replacement of Na+ by Li+ or Eu3+ decreased the specific uptake of 5-HT in JAR cells by 94-100% and that of dopamine in transfected COS-7 cells by 95-99%. The direct effects of Eu3+ (with Na+ present) on the human noradrenaline transporter in SK-N-SH-SY5Y cells were also examined. Eu3+ inhibited noradrenaline uptake into the cells (IC50 2.6 mM) and nisoxetine binding to crude membranes of SK-N-SH-SY5Y cells (IC50 4.7 mM) with similar potencies. Further experiments showed that 4.5 mM EuCl3 in the presence of 150 mM Na+ caused a 3.5-fold increase in the K(m) of noradrenaline and no change in the maximal rate of noradrenaline uptake. EuCl3 (4.5 mM) also caused a pronounced inhibition of the Na(+)-dependent stimulation of noradrenaline uptake by SK-N-SH-SY5Y cells. It can be concluded from these data that, in contrast with the Na+/glucose and Na+/proline cotransporters, the lanthanides cannot substitute for Na+ in the transport of substrates by the monoamine neurotransmitter transporters and that the lanthanides inhibit the latter transporters by interacting with sites of the transporters involved in amine and Na+ binding.