Dual-photosensitizer coupled nanoscintillator capable of producing type I and type II ROS for next generation photodynamic therapy.

The current photodynamic therapy (PDT) is majorly hindered by the shallow penetration depth and oxygen dependency, limiting its application to deep-seated solid hypoxic tumors. Thus, it is meaningful to develop efficient X-ray mediated PDT system capable of generating reactive oxygen species (ROS) under both the normoxic and hypoxic conditions. Herein, we report the synthesis and characterization of nanocomposite, YAG:Pr@ZnO@PpIX with an amalgamation of UV-emitting Y2.99Pr0.01Al5O12 (YAG:Pr) nanoscintillator, and zinc oxide (ZnO) and protoporphyrin IX (PpIX) as photosensitizers. YAG:Pr surface was coated with a ZnO layer (∼10 nm) by atomic layer deposition, and then PpIX was covalently conjugated via a linker to give YAG:Pr@ZnO@PpIX. The photo- and cathodoluminescence analyses gave the evidences of efficient energy transfer from YAG:Pr to ZnO at ∼320 nm, and YAG:Pr@ZnO to PpIX at Soret region (350-450 nm). The nanohybrid was able to produce both, Type I and Type II ROS upon direct and indirect photoactivation with UV365nm and UV290nm, respectively. In vitro cytotoxicity of non-activated YAG:Pr@ZnO@PpIX in mouse melanoma cells revealed low toxicity, which significantly enhanced upon photoactivation with UV365nm indicating the photokilling property of the nanohybrid. Overall, our preliminary studies successfully demonstrate the potential of YAG:Pr@ZnO@PpIX to overcome the limited penetration and oxygen-dependency of traditional PDT.

Bare and nonionic surfactant-functionalized praseodymium oxide nanoparticles: Toxicological studies.

The applications of praseodymium oxide (Pr6O11) nanomaterials in catalysis, oxygen storage materials, and optical devices are the emergent areas that possess an urgent requirement for the toxicological evaluation of these nanomaterials to determine their impact on the ecology. In the present work, we have employed a multiassay approach for the toxicological profiling of bare and nonionic surface-modulated Pr6O11 nanoparticles (NPs). The contemporary analysis in this work has presented a great prospect to develop efficient indicators and inspect the toxic nature of bare and functionalized Pr6O11 NPs. The effect of Pr6O11 NPs was analyzed on germination parameters by the wheat seed germination assay and on algal growth by the paper disc approach. The influence of Pr6O11 NPs on the percentage viability of four different types of bacteria, namely, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Salmonella typhi, was investigated. The substantial effect of different concentrations of Pr6O11 NPs on Allium cepa was investigated at the genomic level by using the chromosomal aberration assay. The functionalized NPs exhibited 41.05%-400% higher biocompatibility by the wheat seed germination assay and 27.1%-47.3% by the A. cepa chromosomal aberration assay than the bare NPs. In algal growth assay and antibacterial activity testing, biocompatibility of the developed functionalized NPs enhanced by 23.1%-37.1% and 10%-70.6%, respectively. The current work evaluated the toxicity of the NPs and measured the competence of the obtained data to characterize possibilities of probable threats, prominence of data requirement, and breaches that must be filled to diminish the ambiguities about the safe use of Pr6O11 NPs.

Comparison of the effects of lanthanum, cerium and praseodymium on rumen fermentation, nutrient digestion and plasma biochemical parameters in beef cattle.

The objectives of the trial were to compare the effects of supplementing rare earth elements (REE) lanthanum (La), cerium (Ce) and praseodymium (Pr) on rumen fermentation, nutrient digestion, methane (CH4) production, nitrogen (N) balance and plasma biochemical parameters in beef cattle. Four Simmental male cattle, aged 12 months, with initial average liveweight of 333 ± 9 kg and fitted with rumen cannulas, were fed with a basal ration composed of concentrate mixture and maize silage. Animals received a basal ration without adding REE (Control) or three treatments, i.e. supplementing LaCl3, CeCl3 or PrCl3 at 204 mg/kg DM to the basal ration, respectively, which were allocated in a 4 × 4 Latin square design. Each experimental period lasted 15 d, consisting of 12 d for pre-treatment and three subsequent days for sampling. Results showed that all tested levels of REE tended to increase neutral detergent fibre digestibility (p = 0.064) and tended to decrease rumen CH4 production (p = 0.056). Supplementing LaCl3 and CeCl3 decreased total N excretion and urinary N excretion, increased N retention (p < 0.05), tended to increase total urinary purine derivatives (PD) (p = 0.053) and microbial N flow (p = 0.095), whereas supplementing PrCl3 did not affect N retention, urinary PD and microbial N flow. No differences were found in the effects of nutrient digestibility, CH4 production and plasma biochemical parameters among LaCl3, CeCl3 and PrCl3. Further trials using graded levels of LaCl3, CeCl3 and PrCl3 in a wide range are needed to obtain more pronounced results for comparing effects of La, Ce and Pr on rumen fermentation and nutrient digestion in beef cattle.

Structural basis for the biological effects of Pr(III) ions: alteration of cell membrane permeability.

The biological effects of rare-earth ions on the organism have been studied using Pr3+ as a probe ion and Escherichia coli cell as a target. Atomic force microscopy (AFM) observation of the surface of E. coli cells shows that the presence of Pr3+ substantially changes the structure of the outer membrane. By induced coupled plasma-mass spectrometry (ICP-MS), more Cu2+ was found in the cells grown in the presence of Pr3+, indicating changes of cell permeability. Using energy dispersive X-ray spectroscopy (EDX), Ca2+ is found on the outer surface of the original cell. It is proposed that Pr3+ can replace Ca2+ from the binding sites because of their close ionic radii and similar ligand speciality.

Weaning pig performance and faecal microbiota with and without in-feed addition of rare earth elements.

Two 6-week feeding trials were conducted on a total of 112 newly weaned piglets to examine the recently reported growth promoting effects of dietary rare earth elements (REE) in European pig production. Rare earth element-diets were supplemented with a REE-citrate premix of lanthanum and the light lanthanoides cerium, praseodymium and neodymium at 200 mg/kg for 6 weeks after weaning. Overall for both trials, growth performance of REE-citrate and control fed piglets did not differ significantly (p > 0.05). An early enhancive tendency for REE-citrate in trial 1 (feed conversion ratio, FCR -3%, p = 0.15) proved irreproducible in trial 2. In the late period of trial 1, in-feed addition of REE-citrate significantly impaired piglet performance (FCR + 8%, p = 0.01). A cultivation-independent molecular approach, polymerase chain reaction-denaturing gradient gel electrophoresis was further applied to assess REE induced alterations in the predominant faecal microbiota from weaning pigs. Calculation of various ecological characteristics does not indicate (p > 0.05) an often discussed selective effect on local microbial composition of dietary REE.

Synthesis, spectroscopic, thermal and antifungal studies on lanthanum(III) and praseodymium(III) derivatives of 1,1-diacetylferrocenyl hydrazones.

A series of new coordination complexes of La(III) and Pr(III) with hydrazones, derived from 1,1-diacetylferrocene and different aromatic acid hydrazides have been synthesized and characterized by elemental analyses, electrical conductance, magnetic moment, IR, (1)H NMR, UV-vis spectra and molar conductance. The thermal behaviour of the complexes under non-isothermal condition was investigated by TG and DTG techniques. The antifungal activity of hydrazones and their corresponding complexes were also investigated.

Effect of praseodymium(III) on zinc(II) species in human interstitial fluid.

A multiphase model of metal ion species in human interstitial fluid was constructed under physiological conditions. The effect of Pr(III) on Zn(II) species was studied. At the normal conditions, Zn(II) species mainly distribute in [Zn(HSA)], [Zn(IgG)], and [Zn(Cys)(2)H](+). With the Pr(III) level increased, the apparent competition of Pr(III) for ligands lead to the redistribution of Zn(II) species.

Computer simulation for effect of Pr(III) on Ca(II) speciation in human interstitial fluid.

A multiphase model of metal ion speciation in human interstitial fluid was constructed and the effect of Pr(III) on Ca(II) speciation was studied. Results show that free Ca2+, [Ca(HCO3)], and [Ca(Lac)] are the main species of Ca(II). Because of the competition of Pr(III) for ligands with Ca(II), the percentages of free Ca2+, [Ca(Lac)], and [Ca(His)(Thr)H3] increase gradually and the percentages of CaHPO4(aq) and [Ca(Cit)(His)H2] decrease gradually with the increase in the total concentration of Pr(III). However, the percentages of [Ca(HCO3)] and CaCO3(aq) first increase and then begin to decrease when the total concentration of Pr(III) exceeds 6.070 x 10-4 M.

Computer simulation for effect of Pr(III) on Ca(II) speciation in human interstitial fluid.

A mutiphase model of metal ion speciation in human interstitial fluid was constructed and the effect of Pr(III) on Ca(II) speciation was studied. Results show that Ca(II) mainly distributes in free Ca2+, [Ca(HCO3)], and [Ca(Lac)]. Because of the competition of Pr(III) for ligands with Ca(II), with the total concentration of Pr(III) rising, the percentages of free Ca2+, [Ca(Lac)] and [Ca(His)(Thr)H3], gradually increase and the percentages of CaHPO4(aq) and [Ca(Cit)(His)H2] gradually decrease. However, the percentages of [Ca(HCO3)] and CaCO3(aq) first increase, and then begin to decrease when the total concentration of Pr(III) exceeds 6.070x10(-4) M.

Study on the performance enhancing effect of rare earth elements in growing and fattening pigs.

A feeding study was performed to investigate possible performance enhancing effects of rare earth elements (REE) in growing and fattening pigs, as well as their influence on the blood serum biochemical changes and the accumulation of REE in the organs of pigs treated with a REE diet for a longer time period. Fourteen crossbred piglets (Deutsche Landrasse x Piétrain) were allotted to two dietary treatments: a control group and the REE-treated group which was supplemented with 300 mg of an REE mixture per kg feed. The REE mixture contained mainly chlorides of lanthanum (La), cerium (Ce) and praseodymium (Pr). The whole feeding period consisted of a 2 months ad libitum feeding period M-I and a 1 month restricted feeding period M-II. It was found that in comparison with the control group, the REE group had a better daily body weight gain of 19% (p < 0.05) in the period M-I and 12% in the period M-II; the REE group also had a better feed conversion ratio of 11% in period M-I and 3% (p > 0.05) in the period M-II. The REE had no significant (p > 0.05) influence on blood serum thyroxine (T(4)), aspartate-amino-transferase (AST), alanine-amino-transferase (ALT), alkaline-phosphatase (AP), total cholesterol, triglyceride, total protein, albumin, glucose, Ca, P, Na, K and Cl. However, serum triiodothyronine (T(3)) in the REE group was significantly (p < 0.01) lower than that in the control group. The accumulation rate of La and Ce in the muscle, liver and kidneys was very low after feeding the REE diet for 3 months. The study indicates the possibility of using rare earth elements as safe and inexpensive alternative performance enhancers for pig production.

Lanthanide ions induce hydrolysis of hemoglobin-bound 2,3-diphosphoglycerate (2,3-DPG), conformational changes of globin and bidirectional changes of 2,3-DPG-hemoglobin's oxygen affinity.

The changes in structure and function of 2,3-diphosphoglycerate-hemoglobin (2,3-DPG-Hb) induced by Ln(3+) binding were studied by spectroscopic methods. The binding of lanthanide cations to 2,3-DPG is prior to that to Hb. Ln(3+) binding causes the hydrolysis of either one from the two phosphomonoester bonds in 2,3-DPG non-specifically. The results using the ultrafiltration method indicate that Ln(3+) binding sites for Hb can be classified into three categories: i.e. positive cooperative sites (N(I)), non-cooperative strong sites (N(S)) and non-cooperative weak sites (N(W)) with binding constants in decreasing order: K(I)>K(S)>K(W). The total number of binding sites amounts to about 65 per Hb tetramer. Information on reaction kinetics was obtained from the change of intrinsic fluorescence in Hb monitored by stopped-flow fluorometry. Fluctuation of fluorescence dependent on Ln(3+) concentration and temperature was observed and can be attributed to the successive conformational changes induced by Ln(3+) binding. The results also reveal the bidirectional changes of the oxygen affinity of Hb in the dependence on Ln(3+) concentration. At the range of [Ln(3+)]/[Hb]<2, the marked increase of oxygen affinity (P(50) decrease) with the Ln(3+) concentration can be attributed to the hydrolysis of 2,3-DPG, while the slight rebound of oxygen affinity in higher Ln(3+) concentration can be interpreted by the transition to the T-state of the Hb tetramer induced by Ln(3+) binding. This was indicated by the changes in secondary structure characterized by the decrease of alpha-helix content.

Rare earth elements--a new generation of growth promoters for pigs?

The present study which includes two feeding experiments was performed to investigate a possible performance enhancing effect of rare earth elements (REF) in piglets. This performance enhancing effect has been described in the Chinese literature for a long time, however, it was never tested under "western conditions". In the first feeding experiment 72 piglets at a mean BW of 7.3 kg were allotted to a control and to 4 REE groups at different levels of lanthanum chloride or an REE mixture containing mainly chlorides of lanthanum, cerium and praseodymium. The experimental period lasted 5 weeks. Positive effects of REE were found on body weight gain as well as on feed conversion ratio of the piglets. Compared to the control group, the daily weight gain was improved by 2 to 5% and feed conversion was better by up to 7%. These effects were, however, not significant. In the second feeding experiment, piglets (mean BW 17.3 kg) were fed for 8 weeks with a similar REE mixture. Significant positive effects of REE were found on both body weight gain and on feed conversion ratio by 19% and 10%, respectively. This is the first time that a performance enhancing effect of REE in pigs under western feeding conditions has been shown. Since the use of antibiotics as growth promoters in animal feed has been restricted in the European Union recently, rare earth elements might be of interest as new, safe and inexpensive alternative performance enhancers.

[Synthesis and anti-influenza virus activities of heteropoly compounds containing rare earth elements].

Tungstoborate and tungstogermanate heteropoly compounds containing rare earth elements with the general formula K15[Ln(BW11O39)2].nH2O and K13[Ln(GeW11O39)2].nH2O, where Ln = La, Ce, Pr, Nd, Sm, have been synthesized and characterized by elemental analysis, IR, 183W NMR spectra. The results of experiments on cytotoxicity and anti-influenza virus activities using cell-cultivation method showed that four compounds among them exhibited good inhibitory effect on influenza virus.

Zeaxanthin (dihydroxy-beta-carotene) but not beta-carotene rigidifies lipid membranes: a 1H-NMR study of carotenoid-egg phosphatidylcholine liposomes.

1H-NMR technique was applied to study liposomes formed with egg-yolk phosphatidylcholine containing as an additional component two carotenoid pigments: beta-carotene or zeaxanthin (dihydrohy-beta-carotene). A strong rigidifying effect of zeaxanthin but not of beta-carotene with respect to hydrophobic core of lipid bilayer was concluded from the carotenoid-dependent broadening of the NMR lines assigned to -CH2- groups and terminal -CH3 groups of lipid alkyl chains. A similar effect of zeaxanthin with respect to polar headgroups was concluded on the basis of the effect of the pigment on the shape of NMR lines attributed to -N+(CH3)3 groups. In contrast, beta-carotene increases motional freedom of lipid polar headgroups. The inclusion of both carotenoids to liposomes resulted in the enhanced penetration of Pr3+ ions to the polar zone of the external layer of a membrane monitored by the splitting of the -N+(CH3)3 signal, the effect of beta-carotene being much more pronounced. Differences in the effect on membrane structure and molecular dynamics observed for beta-carotene and its polar derivative are discussed in terms of organization of a carotenoid-containing lipid membrane.

Effect of agents which modify reticuloendothelial system function on acute phalloidin-induced lethality and hepatotoxicity in mice.

The relationship between reticuloendothelial system (RES) function and acute phalloidin intoxication was studied in mice. Pretreatment with compounds that stimulate (zymosan) or depress (methyl palmitate and praseodymium nitrate, Pr(NO3)3) the RES resulted in protection against phalloidin-induced lethality and hepatotoxicity, as assessed by morphological analysis. However, triolein (which stimulates the RES) was ineffective against phalloidin. The timing of pretreatment with the effective compounds showed a correlation between modified in vivo RES function (phagocytosis) and protection against the toxin. The effects of pretreatment with zymosan and Pr(NO3)3 were further characterized. Hepatic damage induced by phalloidin was significantly decreased by these agents, as judged by morphological analysis as well as by serum aspartate aminotransferase and alanine aminotransferase release. This study also showed that there was no correlation between the capacity of Kupffer cells to produce nitrite and prophylaxis against phalloidin. However, liver cell proliferation was increased by zymosan and Pr(NO3)3 in parallel with protection against the toxin. Furthermore, freshly isolated hepatocytes from zymosan- or Pr(NO3)3-treated mice were less sensitive to phalloidin in vitro. These results indicate that the protective effect of these agents against phalloidin-induced hepatotoxicity may be mediated by their mitogenic properties.

Metabolite transport in rat kidney mitochondria: ornithine/phosphate translocator.

Ornithine uptake by rat kidney mitochondria is here first shown by monitoring the reduction of the intramitochondrial pyridine nucleotides which occurs as a result of metabolism of imported ornithine via ornithine aminotransferase and 1-pyrroline-carboxylate dehydrogenase. Ornithine uptake shows saturation features (Km and Vmax values, measured at 20 degrees C and at pH 7.20, were found to be about 0.85 mM and 23 nmoles/min x mg protein, respectively) and proves to be inhibited by D-ornithine, inorganic phosphate, praseodimium chloride and mersalyl. Neither malate nor glutamate, but phosphate was found to exchange with ornithine. Phosphate efflux caused by externally added ornithine was shown both as revealed by a c colorimetric assay and as continuously monitored by measuring extramitochondrial reduction of NAD+ in the presence of glyceraldehyde-3-phosphate, glyceraldehyde-3-phosphate dehydrogenase, ADP and 3-phosphoglycerate kinase. The role of ornithine carrier in kidney metabolism will also be discussed.

NMR study of the interaction of beta-blockers with sonicated dimyristoylphosphatidylcholine liposomes in the presence of praseodymium cation.

The interaction of a series of beta-adrenoreceptor blocking agents with unilamellar dimyristoylphosphatidylcholine (DMPC) liposomes has been studied by proton nuclear magnetic resonance (1H-NMR) in the presence of praseodymium cation (Pr3+) at 30 degrees C. Addition of Pr3+ increased the splitting of the trimethylammonium group signals arising from the phospholipid molecules located at the internal and external surfaces of the bilayers. Adding Pr3+ caused a considerable downfield shift of the external peak but only a slight upfield shift of the internal peak (approximately 3%). The difference in chemical shift of the external and internal peaks (delta Hz) increased linearly as a function of Pr3+ concentration up to 10 mM. The addition of beta-blockers reversed the effect of Pr3+, and propranolol exerted the most pronounced effect, causing complete reversal of the splitting at a concentration of 5 mM. Much higher concentrations of other beta-blockers were required to displace Pr3+. A linear correlation between Pr3+ displacement (P) and logarithm of the apparent partition coefficient (K'm) in DMPC liposomes was obtained for hydrophobic beta-blockers, but hydrophilic beta-blockers did not fit this correlation. It appears that beta-blockers that have ortho or meta substitution require penetration of the liposome bilayers before significant polar group interaction can occur. On the other hand, beta-blockers that have para substitution and low K'm values are able to interact with the polar surfaces of the liposomes without penetration to cause displacement of Pr3+.

Bilayer asymmetry in lysophosphatidylcholine/cholesterol (1:1) vesicles. A phosphorus-31 NMR study.

Prolonged sonication (3 h) of equimolar amounts of lysophosphatidylcholine (lysoPC) and cholesterol (chol) produces small unilamellar vesicles. Phosphorus-31 NMR (32.20 MHz) of the vesicles gave rise to a single peak (40.5 ppm) which was split upon addition of lanthanide ions. An additional, more intense signal appeared downfield near 51.0 ppm due to 2.4 mM Pr3+, upfield near 34.3 ppm due to 5 mM Yb3+. The more intense signals responsive to paramagnetic ions were assigned to lysoPC located in the outer vesicle leaflet; the signal not shifted by the ions was assigned to inside lysoPC. Based on peak intensities, an outside-to-inside lysoPC ratio (Ro/i) of 6.5-6.6 was determined. Essentially the same Ro/i values (6.6-6.8) were obtained when Pr3+ was present only in the vesicle interior or when Pr3+ was on the inside and Pr3+ and Yb3+ were on the outside. Ion leakage did not occur. Our data demonstrate that lysoPC/chol (1:1) vesicles are drastically asymmetric and that lysoPC shows a distinct preference for the outer bilayer leaflet.

Effect of praseodymium chloride on liver microsomal enzymes of rats.

A single i.v. dose (5 mg/kg) of a light lanthanon, praseodymium, prolonged the duration of hexobarbital-induced sleep and zoxazolamine-induced paralysis, as well as it modified pharmacokinetic parameters of hexobarbital and zoxazolamine, in rats. Half-lives (t1/2) and area under the curve (AUC) were increased, while elimination coefficient (beta) and clearance (Cl) were decreased. However, in daily doses of 1 mg/kg i.p. for 15 days, praseodymium did not alter pharmacological effects and pharmacokinetic parameters. The in vitro hydroxylation of hexobarbital and zoxazolamine by liver microsomes was inhibited when the animals were treated previously with a single i.v. dose (5 mg/kg) of praseodymium chloride. In these animals, the amount of cytochromes P-450 and b5 were reduced significantly, whereas that of NADPH-cytochrome c reductase remained unchanged. The pretreatment of animals with phenobarbital normalized the microsomal enzyme impairment caused by praseodymium.