Pr3+ doped NaYF4 and LiYF4 nanocrystals combining visible-to-UVC upconversion and NIR-to-NIR-II downconversion luminescence emissions for biomedical applications.

Lanthanide-doped fluoride nanocrystals (NCs) are known to exhibit unique optical properties, such as upconversion and downconversion luminescence (UCL and DCL), which can be employed for various applications. In this work, we demonstrate that by doping praseodymium(III) and ytterbium(III) ions (Pr3+ and Yb3+) into a nanosized fluoride matrix (i.e. NaYF4 and LiYF4), it is possible to combine their UCL and DCL properties that can be concurrently used for biomedical applications. In particular, the emissive modes combined in a single nanoparticle co-doped with Pr3+ and Yb3+ include DCL emission (excited at 980 nm and peaked at 1320 nm), which can be used for near infrared (NIR) DCL bioimaging in the NIR-II window of biological tissue transparency (∼1000-1350 nm) and UCL emission (excited at 447 nm and peaked at 275 nm) that can be employed for germicide action (via irradiation by light in the UVC range). A possibility of the latter was demonstrated by the denaturation of double-stranded DNA (dsDNA) into single-stranded ones that was caused by the UVC UCL emission from the NCs under 447 nm irradiation; it was evidenced by the hyperchromicity observed in the irradiated dsDNA solution and also by a fluorometric analysis of DNA unwinding (FADU) assay. Concurrently, the possibility of NIR-II luminescence bioimaging through biological tissues (bovine tooth and chicken flesh) was demonstrated. The proposed concept paves a way for NIR-II imaging guided antimicrobial phototherapy using lanthanide-doped fluoride nanocrystals.

Apatite matrix substituted with biologically essential rare earth elements as an artificial hard tissue substitute: Systematic physicochemical and biological evaluation.

Hydroxyapatite (HAP) forms the main inorganic component of natural bone and hence has been widely use in implant applications. Ionic substitutions in apatite also gains enormous interest during the recent years due to the crucial role played by these elements in the biological process. In this context, the least investigated elements namely lanthanum (La3+ ) and praseodymium (Pr3+ ) have been selected as a potential substitutions in apatite. The results from the analytical techniques confirm the phase purity of the HAP and its ability holds the substitutions at its lattice. Morphological analysis unveils the presence of agglomerated spheroids notwithstanding the ion concentration of substituents. EDX spectra affirm the presence of La and Pr alongside the determined Ca/P atomic ratio of 1.67. La3+ and Pr3+ presence envisaged the good antibacterial efficiency against the tested microbes and further demonstrated the biocompatibility nature from the cytotoxicity analysis.

Distribution Characteristics of Rare Earth Elements and Selenium in Hair of Centenarians Living in China Longevity Region.

In order to explore the characteristics of the rare earth elements (REEs) and selenium (Se) among the Chinese centenarians, the concentrations of REE and Se were detected in the hair of healthy centenarians living in typical Chinese longevity region, and the influences of physiological conditions and behavior on the concentrations of REE and Se were assessed. The average values of light RE (LRE) and heavy RE (HRE) are 31.87 and 11.12 ng/g. Female centenarians had higher concentrations of lanthanum (La), praseodymium (Pr), gadolinium (Gd), terbium (Tb), erbium (Er), thulium (Tm), yttrium (Y), and Se but lower levels of cerium (Ce), neodymium (Nd), samarium (Sm), europium (Eu), dysprosium (Dy), holmium (Ho), ytterbium (Yb), and lutetium (Lu). Except for Ce, the higher the age, the lower the REE and Se content were. Smoking was positively associated with Dy, Er, and Yb levels, whereas drinking habits showed no significant effect on all the elements. Elderly individuals who ate smoked and pickled food and who consumed high amounts of salt had higher levels of REE and Se in their hair, and centenarians who consumed egg and milk had higher Se and REE in the hair than did the non-eaters. This comprehensive study on the REE and Se concentrations among the healthy centenarians can provide scientific support for shaping a healthy aging society.

A novel conformal superficial high-dose-rate brachytherapy device for the treatment of nonmelanoma skin cancer and keloids.

PURPOSE: To develop a novel conformal superficial brachytherapy (CSBT) device as a treatment option for the patient-specific radiation therapy of conditions including superficial lesions, postsurgical positive margins, Dupuytren's contractures, keloid scars, and complex anatomic sites (eyelids, nose, ears, etc.). METHODS AND MATERIALS: A preliminary CSBT device prototype was designed, built, and tested using readily available radioactive seeds. Iodine-125 (125I) seeds were independently guided to the treatment surface to conform to the target. Treatment planning was performed via BrachyVision Planning System (BPS) and dose distributions measured with Gafchromic EBT3 film. Percent depth dose curves and profiles for Praseodymium-142 (142Pr), and Strontium-90/Yttrium-90 (90Sr-90Y) were also investigated as potential sources. Results achieved with 90Sr-90Y and electron external beam radiation therapy were compared and Monte Carlo N-Particle eXtended 2.6 simulations of 142Pr seeds were validated. RESULTS: BPS was able to predict clinical dose distributions for a multiple seeds matrix. Calculated and measured doses for the 125I seed matrix were 500 cGy and 473.5 cGy at 5 mm depth, and 171.0 cGy and 201.0 cGy at 10 mm depth, respectively. Results of 90Sr-90Y tests demonstrate a more conformal dose than electron EBRT (1.6 mm compared to 4.3 mm penumbra). Measured 142Pr doses were 500 cGy at surface and 17.4 cGy at 5 mm depth. CONCLUSIONS: The CSBT device provides a highly conformal dose to small surface areas. Commercially available BPS can be used for treatment planning, and Monte Carlo simulation can be used for plans using beta-emitting sources and complex anatomies. Various radionuclides may be used in this device to suit prescription depths and treatment areas.

Efficient visible laser emission of GaN laser diode pumped Pr-doped fluoride scheelite crystals.

In the present work we report on the growth, spectroscopy and laser results of diode pumped Pr-doped LiYF(4), LiLuF(4) and LiGdF(4) fluoride, scheelite-type structure crystals. We measured the polarisation dependent absorption and emission properties as well as the decay time of the (3)P(0) level. Exploiting the (3)P(2) absorption around 444 nm, we obtained efficient laser emission under GaN laser diode pumping on several transitions from the green to the near infrared wavelength range.

An NMR method towards the routine chiral determination of natural products.

State-of-the-art structure elucidation and dereplication of natural products is incomplete without the determination of enantiomeric purity, especially when compounds are to be biologically evaluated. An NMR procedure is presented in order to distinguish and determine enantiomers in natural product samples. The method is also of value in the structure elucidation process by providing information, which is otherwise of a non-routine nature. Using enantiomeric 1-acetoxychavicol acetates and carvones as model compounds, this study presents a chiral NMR procedure that allows distinction and determination of chiral antipodes of natural products in a routine set-up.

Non-invasive MR thermometry by 2D spectroscopic imaging of the Pr[MOE-DO3A] complex.

Future progress in regional hyperthermia requires a practical method for non-invasive thermometry. In magnetic resonance tomography, spin density, T1 relaxation time, diffusion coefficient and proton resonance frequency are candidates to measure temperature distributions. When used clinically in the pelvic region, all these methods are compromized by artifacts arising from different tissues, tissue alterations under hyperthermia, physiological and random movements, inhomogeneities, drift phenomena, and field instabilities. In this study a paramagnetic complex was evaluated, Pr[MOE-DO3A], with praseodymium as central atom, similar to common gadolinium containing MRI contrast media. The temperature dependence of its methoxy side group approximately -24 ppm downfield from the water resonance at 25 degrees C was employed to determine 2-D temperature distributions in a cylindrical agar phantom containing 9.5 mM of Pr[MOE-DO3A]. The phantom was heated externally through a water jacket creating a stationary temperature distribution throughout the phantom. At first, the correlation between temperature and the chemical shift of the methyl group of the lanthanide complex Pr[MOE-DO3A] was determined. Calibration curves obtained exhibited a linear relationship of 0.12 +/- 0.01 ppm/degree C, nearly independent from the surrounding medium. Local temperature distributions were determined employing the spatially resolved method of spectroscopic imaging (SI). 2-D spectroscopic images for three orthogonal slices were obtained by narrow-band excitation and 16 phase encoding steps in two dimensions. The FOV was 180 mm and the slice thickness in all cases was 20 mm for maximal spatial temperature resolution (11.2 x 11.2 mm2). The results indicate a measurement time of about 5s per acquisition under the following conditions: An estimated concentration of 1 mmol/l, a reduced matrix size of 8 x 8, and a reduced repetition time of 3 x T1 (TR approximately 85 ms). Those SI measurements produced a SNR of approximately 4 per acquisition, a measurements duration of 10-20 s, equivalent to two to four acquisitions per spectrum, seem sufficient for online temperature monitoring during hyperthermia. The in vitro data suggest the spectroscopic temperature measurement utilizing a temperature-sensitive Pr[MOE-DO3A] complex with a therapeutically realistic concentration of 1 mmol/l to be suitable for clinical use. Compared to the methods tested so far (rho, T1, diffusion, proton resonance), the method presented has the unique advantage of being less susceptible to artifacts. The competing methods of non-invasive thermometry employing magnetic resonance imaging are currently being investigated using the same experimental setup.

[Thermometry by measuring the chemical shift of lanthanide complex]. / Thermometrie durch Messung der chemischen Verschiebung eines Lanthanidenkomplexes.

BACKGROUND: In the long-term, non-invasive thermometry is vital for the continued clinical and technological development of regional hyperthermia. In magnetic resonance tomography. T1 relaxation time, diffusion and proton resonance frequency are used to measure temperature distributions. When used clinically in the pelvic region, all of these methods are plagued with errors and artefacts on account of the tissue relationships, tissue changes under hyperthermia, physiological and stochastic movements, inhomogeneities, drift phenomena and instabilities. MATERIAL AND METHOD: We tested the relationship between the temperature and the chemical shift of a methyl group of a lanthanide complex with central atom praseodymium (Pr-MOE-DO3A. Schering AG). To do this we used cylindrical phantoms containing a 5-mmol-solution of this temperature-sensitive substance. High resolution spectra and relaxation times were determined in a Bruker AMX at 11.5 T. A calibration curve was then recorded by a Siemens Magnetom SP63 at 1.5 T. Local temperature distributions were determined using the chemical shift imaging method, with a matrix size of 16 x 8 and a narrow-band excitation pulse. The temperature distribution was created using a Nd:YAG laser applicator. RESULTS: At a distance of -25.7 ppm from the water line, we found a singlet line with a temperature-dependent chemical shift of 0.13 ppm/C. In the phantom experiment we found that the chemical shift had a linear relationship with a gradient independent of the surroundings, and a temperature resolution of +/-0.6 degree C. With a concentration of 1 mmol/l, a matrix size of 8 x 8 and a measurement period of 5 s per acquisition, phantom measurements using the CSI method produced a signal to noise ratio of 3.5 per acquisition, i.e a measurement period of 10 to 20 s per spectrum. CONCLUSIONS: Our in vitro data show that spectroscopic temperature measurement using a temperature-sensitive praseodymium complex with a therapeutically practical concentration of 1 mmol/l already appears to be suitable for clinical use Compared with the methods tested so far (T1, diffusion, proton resonance), this method has the special advantage of not being very susceptible to artefacts. The competing methods of non-invasive thermometry using magnetic resonance tomography/spectroscopy will be investigated next.

Skin dose calculations for uranium fuel particles below 500 microns in diameter.

Two different methods for skin dose calculations, VARSKIN Mod 2 and PSS are compared for a spherical uranium fuel particle (diameter 1-500 microns) deposited on the skin. Nuclide-specific beta dose rate at different skin depths for a particle of unit activity is determined as a function of particle size. Both methods show that the effects of self-shielding must be included in the dose calculations for low and medium energy beta emitters. Skin dose rate is drastically overestimated when point source approximation is used. For high energy beta emitters (e.g., 90Y, 106Rh, and 144Pr) the volume source can be approximated as a point source. The difference in doses is then below 20% for particles up to 100 microns in diameter. The models give equal results deep in the skin (in terms of range of the beta particles). The reason is that the correction due to the diminished backscattering in air-tissue interface is insignificant at large distances. For three-dimensional sources the backscattering correction should be introduced in the VARSKIN Mod 2.

Clastogenicity of lanthanides--induction of micronuclei in root tips of Vicia faba.

The clastogenic property of two lanthanides, Praseodymium and Neodymium, was evaluated by scoring the frequencies of micronucleated cells in the interphase and chromosome/chromatid aberrations at ana-telophases in root tips of Vicia faba L. The significant increase in the frequency of micronucleated cells coupled with the increase in the frequency of chromosome/chromatid bridges and lagging chromosomes/chromatids suggest that these two are clastogenic for Vicia faba root cells.

Protective activity of silipide on liver damage in rodents.

The activity of silipide, a silybin-phosphatidylcholine complex (IdB 1016), was tested in different models of liver damage in rodents. After oral administration, silipide exhibited a significant and dose-related protective effect against the hepatotoxicity induced by CCl4, praseodymium, ethanol and galactosamine. The ED50 values for inhibition of the rise in ASAT and ALAT levels caused by CCl4 and praseodymium and for antagonism of the increase in liver triglycerides caused by ethanol ranged from 93 to 156 mg/kg (as silybin). At a dose of 400 mg/kg (as silybin), silipide was also active in protecting against paracetamol-induced hepatotoxicity. Silybin and phosphatidylcholine at doses equivalent to those contained in the active doses of silipide failed to show any significant protective activity in these models. The liver protective effect of silipide is probably related to its antioxidant activities and to a stimulating effect on the hepatic synthesis of RNA and proteins.

Lanthanide-induced phosphorus-31 NMR downfield chemical shifts of lysophosphatidylcholines are sensitive to lysophospholipid critical micelle concentration.

Lysophosphatidylcholine (lysoPC) monomers or micelles in water give rise to a narrow, isotropic phosphorus-31 NMR signal (40.6 ppm; v1/2 1.7 Hz; 32.2 MHz). Upon addition of praseodymium ions, the phosphorus signals are shifted downfield. However, the downfield shifts for the longer-chain lysophosphatidylcholines, which exist in the aggregated state, are far greater than those for the shorter-chain homologues, which exist as monomers. At a Pr3+/lysoPC molar ratio of 0.5, the signals of C12lysoPC through C18lysoPC were shifted by 12.1 ppm, whereas the signals of C6lysoPC and C8lysoPC were shifted by only 2.26 ppm. This very pronounced difference in lanthanide-induced downfield shifts between micelles and monomers can be utilized to determine with accuracy lysoPC critical micelle concentrations (CMC) from downfield shift-vs.-concentration plots. The CMC values we determined were 57 mM for C8lysoPC, 5.7 mM for C10lysoPC, and 0.6 mM for C12lysoPC. The shift reagent phosphorus-31 nuclear magnetic resonance technique particularly lends itself to the measurement of CMC values in the millimolar and high micromolar range. The method can equally be used for measuring critical micelle concentrations of short-chain phosphatidylcholines.

Metal ion activation of galactosyltransferase.

Galactosyltransferase, which functions as the catalytic component of lactose synthase and in the glycosylation of glycoproteins, has been previously reported to have an absolute dependence on Mn2+ for activity, with a Kd for Mn2+ (10(-3) M) 2 to 3 orders of magnitude greater than the physiological range of Mn2+ concentrations (v 10(-6) M). Reinvestigation of the metal ion dependence of this enzyme has shown that Zn2+, Cd2+, Fe2+, Co2+, and Pr3+ also produce activation, although with lower activities at saturation than that attained with Mn2+. Velocity against metal ion concentration curves for all metals, including Mn2+, are sigmoid, suggesting the presence of two or more activating metal binding sites on the enzyme. The presence of two sites is confirmed by studies using both Mn2+ and Ca2+. While galactosyltransferase is inactive in the presence of Ca2+ alone, at low concentrations of Mn2+ (10(-5) M), enzyme activity is stimulated by Ca2+. A more detailed investigation by steady state kinetics has revealed that there is a tight binding site for Mn2+ (site I: Kd of 2 X 10(-6) M) from which Ca2+ is excluded, and a site at which Ca2+ can replace Mn2+ (site II: Kd for Ca2+ of 1.76 X 10(-3) M), to which metal binding has a specific synergistic effect on UDP-galactose binding, possibly as a result of the formation of an enzyme-Ca2+-UDP-galactose bridge complex. The site I Mn2+, site II Ca2+-activated enzyme has a maximum velocity similar to that of the Mn2+-activated enzyme, and is the enzyme form that must act in lactose synthesis in vivo. A trypsin-degraded form of galactose transferase (galactosyltransferase-T) (Powell, J.T., and Brew, K. (1974) Eur. J. Biochem. 48, 217-228) appears to lack site I and is activated by Ca2+ in the absence of Mn2+.