Effect of the dose on the toxicokinetics of a quaternary mixture of rare earth elements administered to rats.

Large human biomonitoring studies are starting to assess exposure to rare earth elements (REEs). Yet, there is a paucity of data on the toxicokinetics of these substances to help interpret biomonitoring data. The objective of the study was to document the effect of the administered dose on the toxicokinetics of REEs. Male Sprague-Dawley rats were injected intravenously with 0.3, 1 or 10 mg/kg body weight (bw) of praseodynium chloride (PrCl3), cerium chloride (CeCl3), neodymium chloride (NdCl3) and yttrium chloride (YCl3) administered together as a mixture. Serial blood samples were withdrawn up to 72 h following injection, and urine and feces were collected at predefined time intervals up to 7 days post-dosing. The REEs were measured by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). For a given REE dose, the time courses in blood, urine and feces were similar for all four REEs. However, the REE dose administered significantly impacted their kinetics, as lower cumulative excretion in urine and feces was associated with higher REE doses. The fraction of REE remaining in rat tissues at the terminal necropsy on post-dosing day 7 also increased with the dose administered, most notably in the lungs and spleen at the 10 mg/kg bw dose. The toxicokinetic parameters calculated from the blood concentration-time profiles further showed significant increases in the mean residence time (MRTIV) for all four REEs at the 10 mg/kg bw dose. The shift in the REE kinetics at high dose may be explained by a higher retention in lysosomes, the main organelle responsible for accumulation of these REEs in different tissues.

Laser-induced breakdown spectroscopy as a straightforward bioimaging tool for plant biologists; the case study for assessment of photon-upconversion nanoparticles in Brassica oleracea L. plant.

The main purpose of this work is to thoroughly describe the implementation protocol of laser-induced breakdown spectroscopy (LIBS) method in the plant analysis. Numerous feasibility studies and recent progress in instrumentation and trends in chemical analysis make LIBS an established method in plant bioimaging. In this work, we present an easy and straightforward phytotoxicity case study with a focus on LIBS method. We intend to demonstrate in detail how to manipulate with plants after exposures and how to prepare them for analyses. Moreover, we aim to achieve 2D maps of spatial element distribution with a good resolution without any loss of sensitivity. The benefits of rapid, low-cost bioimaging are highlighted. In this study, cabbage (Brassica oleracea L.) was treated with an aqueous dispersion of photon-upconversion nanoparticles (NaYF4 doped with Yb3+ and Tm3+ coated with carboxylated silica shell) in a hydroponic short-term toxicity test. After a 72-hour plant exposure, several macroscopic toxicity end-points were monitored. The translocation of Y, Yb, and Tm across the whole plant was set by employing LIBS with a lateral resolution 100 µm. The LIBS maps of rare-earth elements in B.oleracea plant grown with 50 µg/mL nanoparticle-treated and ion-treated exposures showed the root as the main storage, while the transfer via stem into leaves was minimal. On the contrary, the LIBS maps of plants exposed to the 500 µg/mL nanoparticle-treated and ion-treated uncover slightly different trends, nanoparticles as well as ions were transferred through the stem into leaves. However, the main storage organ was a root as well.

The potential role of nanoyttria in alleviating oxidative stress biomarkers: Implications for Alzheimer's disease therapy.

Alzheimer's disease (AD) is a fatal neurodegenerative disease that requires immediate attention. Oxidative stress that leads to the generation of reactive oxygen species is a contributing factor to the disease progression by promoting synthesis and deposition of amyloid-ß, the main hallmark protein in AD. It has been previously demonstrated that nanoyttria possesses antioxidant properties and can alleviate cellular oxidative injury in various toxicity and disease models. This review proposed that nanoyttria could be used for the treatment of AD. In this paper, the evidence on the antioxidant potential of nanoyttria is presented and its prospects on AD therapy are discussed.

Multi-organ Toxicity Attenuation by Cerium Oxide and Yttrium Oxide Nanoparticles: Comparing the Beneficial Effects on Tissues Oxidative Damage Induced by Sub-acute Exposure to Diazinon.

BACKGROUND: Excessive use of diazinon, as an organophosphate pesticide (OP), contributes to cytotoxic and pathologic cellular damage and, in particular, oxidative stress. However, metal-oxide nanoparticles (NPs), such as cerium oxide (CeO2) and yttrium oxide (Y2O3), with the property of free radical scavenging demonstrated beneficial effects in the alleviation of oxidative stress biomarkers. OBJECTIVE: The aims of this study include evaluating beneficial effects of CeO2 NPs, Y2O3 NPs, and their combination against diazinon-induced oxidative stress in different tissues of brain, heart, lung, kidney, liver, and spleen. METHODS: Eight randomized groups of 6 adult male Wistar rats were formed. Each group of rats administered a different combination of diazinon, CeO2 and Y2O3 NPs daily and levels of oxidative stress markers, such as reactive oxygen species (ROS), lipid peroxidation (LPO), total thiol molecules (TTM) and total anti-oxidant power (TAP) and catalase enzyme, were measured after 2 weeks of the treatment. RESULTS: Measurements of the mentioned markers in the brain, heart, lung, kidney, liver, and spleen showed that the administration of NPs could significantly alleviate the oxidative stress induced by diazinon. However, the findings of this study illustrated that the combination of both CeO2 and Y2O3 NPs led to a better reduction in oxidative stress markers. CONCLUSION: Sub-acute exposure of diazinon in rats led to increased levels of oxidative stress markers in pivotal tissues such as the brain, heart, lung, kidney, liver, and spleen. CeO2 and Y2O3 NPs neutralize the oxidative stress to compensate diazinon-induced tissue damages. Lay Summary: Organophosphate pesticides (OPs), which are mainly used for pest control, are responsible for the entry of pesticides into the human food cycle. Organophosphate such as diazinon increases the molecular biomarkers of oxidative stress inside the cells of vital tissues such as the heart, liver, lungs, etc. Metal oxide nanoparticles (NPs) such as cerium oxide (CeO2) and yitrium oxide (Y2O3) can have free radical scavenging potential under oxidative stress and through various mechanisms. Although these nanoparticles reduce oxidative stress, it should be borne in the design of the study that additional doses of these substances reverse the beneficial effects.

Oleogel-mediated transdermal delivery of white emitting NaYF4 conjugated with Rose Bengal for the generation of reactive oxygen species through NIR-upconversion.

The transdermal route for the delivery of therapeutic agents to the inner skin tissues for non-invasive photodynamic therapy; though constitutes a desired modality for treating skin cancer, the success has been limited due to the insurmountable nature of the stratum corneum (SC). In this context, for the first time we report the localization of photosensitizer-conjugated upconversion (UC) particles to the deeper dermal region by overcoming SC through an oleogel-mediated transport mechanism for NIR-induced photodynamic production of reactive oxygen species (ROS). We developed soybean oil and stearic acid based oleogels by incorporating photoluminescent white light emitting NaYF4 (WEN) upconversion (UC) particles conjugated with Rose Bengal (RB), termed as WEN-RB-G. Similarly, we fabricated another type of oleogel by incorporating Li+ doped WEN based UC particles (RB conjugated), with 10 times more photoluminescence intensity, termed as LiWEN-RB-G. Based on the skin permeation enhancing effect of the constituents of the oleogels, we demonstrated the permeation of these two types of conjugated particles in microgram scale through the full thickness of the pig ear skin model within 48 h. The localization of the conjugated particles throughout the skin tissue including dermal and epidermal region was confirmed by confocal microscopy. We also conducted a comparative assessment on WEN-RB-G and LiWEN-RB-G for the suitability of ROS generation and bioimaging under NIR activation. The 'proof of principle' concept reported here is expected to frame a gateway in future for NIR-induced photo-theranostics targeting skin cancer.

Comparative study of toxicological assessment of yttrium oxide nano- and microparticles in Wistar rats after 28 days of repeated oral administration.

Despite their enormous advantages, nanoparticles (NPs) have elicited disquiet over their safety. Among the numerous NPs, yttrium oxide (Y2O3) NPs are utilised in many applications. However, knowledge about their toxicity is limited, and it is imperative to investigate their potential adverse effects. Therefore, this study explored the effect of 28 days of repeated oral exposure of Wistar rats to 30, 120 and 480 mg/kg body weight (bw) per day of Y2O3 NPs and microparticles (MPs). Before initiation of the study, characterisation of the particles by transmission electron microscopy, dynamic light scattering, Brunauer-Emmett-Teller and laser Doppler velocimetry was undertaken. Genotoxicity was evaluated using the comet and micronucleus (MN) assays. Biochemical markers aspartate transaminase, alanine transaminase, alkaline phosphatase, malondialdehyde, superoxide dismutase, reduced glutathione, catalase and lactate dehydrogenase in serum, liver and kidney were determined. Bioaccumulation of the particles was analysed by inductively coupled plasma optical emission spectrometry. The results of the comet and MN assays showed significant differences between the control and groups treated with 120 and 480 mg/kg bw/day Y2O3 NPs. Significant biochemical alterations were also observed at 120 and 480 mg/kg bw/day. Haematological and histopathological changes were documented. Yttrium (Y) biodistribution was detected in liver, kidney, blood, intestine, lungs, spleen, heart and brain in a dose- and the organ-dependent manner in both the particles. Further, the highest levels of Y were found in the liver and the lowest in the brain of the treated rats. More of the Y from NPs was excreted in the urine than in the faeces. Furthermore, NP-treated rats exhibited much higher absorption and tissue accumulation. These interpretations furnish rudimentary data of the apparent genotoxicity of NPs and MPs of Y2O3 as well as the biodistribution of Y. A no-observed adverse effect level of 30 mg/kg bw/day was found after oral exposure of rats to Y2O3 NPs.

Effect of Er:YAG Laser for Women with Stress Urinary Incontinence.

PURPOSE: The aim of our study is to assess efficacy of noninvasive erbium-doped yttrium aluminium garnet laser (Er:YAG laser) for female stress urinary incontinence (SUI). MATERIALS AND METHODS: Forty-one women with SUI were included in the study and scheduled for vaginal Er:YAG laser treatment. The procedure was performed with a 2940 nm, Er:YAG laser (Fotona Smooth ™ XS, Fotona, Ljubljana, Slovenia), designed to heat up the vaginal mucosa to around 60°C. All subjects had a baseline and 6 months' posttreatment assessment that included perineal sonography and lower urinary tract symptoms. RESULTS: Significant improvements in both urinary frequency and incontinence were found 6 months after Er:YAG laser treatment when compared to the baseline results (p<0.001). The battery of questionnaires administered to patients, including the UDI-6, IIQ-7, OABSS, and POPDI-6, all showed significant improvement posttreatment (P < 0.001). The treatment efficacy for the vaginal Er:YAG laser for SUI at 6 months posttreatment was 75.5% (31/41). Bladder neck mobility by perineal ultrasonography decreased significantly (16.1 ± 6.4 mm to 10.5 ± 4.6 mm) after treatment (p=0.039). No permanent adverse events were found. CONCLUSIONS: The Er:YAG vaginal laser seems to be a safe and efficacious treatment for women with mild to moderate SUI, this being partly related to the decrease of bladder neck mobility following laser treatment.

Hormetic Effects of Yttrium on Male Sprague-Dawley Rats.

To evaluate hormesis induced by Yttrium (Y) nitrate in male rats, Y was offered to F0 mother rats and F1 offspring at concentrations of 0, 20, 80, and 320 ppm daily from gestational day (GD) 0 through postnatal day 70 (PND 70). The F1 offspring were evaluated with respect to motor function, learning and memory, and histopathology. Administration of Y improved motor function in a dose dependent manner. In the 20 ppm group, body weight and spatial learning and memory were increased, while the latter was decreased in the 320 ppm group. Additionally, in the 20 ppm and 80 ppm, but not the 320 ppm groups, Y reduced the anogenital distance, which indicated an anti-androgen effect. These results suggest that Y follows a hormetic concentration-related trend with an inverted U-shape.

Subchronic toxicity study of yttrium nitrate by 90-day repeated oral exposure in rats.

Concerns regarding the adverse effects of long-term exposure to low levels of rare earth elements (REEs) from foods on human health have arisen in recent years. Nevertheless, no official acceptable daily intake (ADI) has yet been proposed for either total REEs or individual REE. In accordance with the Organization for Economic Co-operation and Development (OECD) testing guideline, the present study was undertaken to evaluate the subchronic toxicity of yttrium, a representative heavy REE with higher contaminated level in foods in China, to achieve a no observed adverse effect level (NOAEL) which is a critical basis for the establishment of an ADI. Yttrium nitrate was orally administered to rats at doses of 0, 10, 30 and 90 mg/kg/day for 90 days followed by a recovery period of 4 weeks. The following toxicity indices were measured: mortality, clinical signs, daily food consumption and weekly body weight; urinalysis, hematology, blood coagulation, clinical biochemistry and histopathology at the end of administration and recovery periods. No toxicologically significant changes were found in any yttrium-treated group as compared to the concurrent control group. Under the present experimental condition, the NOAEL in rats was thus set at 90 mg/kg for yttrium nitrate, i.e. 29.1 mg/kg for yttrium.

Protective effects of cerium oxide and yttrium oxide nanoparticles on reduction of oxidative stress induced by sub-acute exposure to diazinon in the rat pancreas.

Diazinon is a kind of organophosphorus (OP) compound that is broadly used against different species of insects and pests. Oxidative stress can occur at very early stages of diazinon exposure and the pancreas is one of the main target organs for toxicity by diazinon. The aim of this study was to evaluate the protective effects of cerium oxide nanoparticles (CeO2 NPs) and yttrium oxide nanoparticles (Y2O3 NPs) against the pancreatic damage from sub-acute exposure of diazinon. Diazinon at a dose of 70mg/kg/day was given through gavage to rats once a day. Along with diazinon, trace amounts of CeO2 NPs and Y2O3 NPs (35mg/kg and 45mg/kg per day, respectively) were administered by intraperitoneal injection once a day for 2 weeks. Animals weight and blood glucose were measured during the treatment, and oxidative stress biomarkers, diabetes physiology, function and viability of cells were investigated at the end of the treatment in serum and pancreas tissues. Apoptosis of islets was examined by the flow cytometry. The high blood glucose level and significant weight loss resulting from diazinon were modified as a result of the application of the NPs. A significant recovery in oxidative stress markers, pro-insulin, insulin, C-peptide, adenosine diphosphate/adenosine triphosphate (ATP/ADP) ratio, caspase-3 and -9 activities and apoptosis-necrosis in the islets was observed. In conclusion, administration of CeO2 NPs or Y2O3 NPs only or their combination with suitable and defined dose will help to overcome the consequences from oxidant agents.

Near infrared light-mediated photoactivation of cytotoxic Re(i) complexes by using lanthanide-doped upconversion nanoparticles.

Platinum-based chemotherapy, although it has been well proven to be effective in the battle against cancer, suffers from limited specificity, severe side effects and drug resistance. The development of new alternatives with potent anticancer effects and improved specificity is therefore urgently needed. Recently, there are some new chemotherapy reagents based on photoactive Re(i) complexes which have been reported as promising alternatives to improve specificity mainly attributed to the spatial and temporal activation process by light irradiation. However, most of them respond to short-wavelength light (e.g. UV, blue or green light), which may cause unwanted photo damage to cells. Herein, we demonstrate a system for near-infrared (NIR) light controlled activation of Re(i) complex cytotoxicity by integration of photoactivatable Re(i) complexes and lanthanide-doped upconversion nanoparticles (UCNPs). Upon NIR irradiation at 980 nm, the Re(i) complex can be locally activated by upconverted UV light emitted from UCNPs and subsequently leads to enhanced cell lethality. Cytotoxicity studies showed effective inactivation of both drug susceptible human ovarian carcinoma A2780 cells and cisplatin resistant subline A2780cis cells by our UCNP based system with NIR irradiation, and there was minimum light toxicity observed in the whole process, suggesting that such a system could provide a promising strategy to control localized activation of Re(i) complexes and therefore minimize potential side effects.

Combined vitamin C sonophoresis and neodymium-doped yttrium aluminum garnet (NdYAG) laser for facial hyperpigmentation: An outcome observation study in Asian patients.

BACKGROUND: The neodymium-doped yttrium aluminum garnet (NdYAG) laser therapy has been a popular technique for facial rejuvenation but certain adverse effects like post-inflammatory hyperpigmentation are issues of concern to Asian patients. AIMS: To assess the outcome following combined treatment with vitamin C sonophoresis and NdYAG laser, in selected cases of facial hyperpigmentation. METHODS: Twenty three women with dyschromia or melasma who had undergone five sessions of Q-switched NdYAG laser therapy followed by transdermal delivery of vitamin C via sonophoresis were selected after a retrospective review of case records. The objective and subjective clinical outcomes and the side effects, including erythema, scaling, pruritus, dryness and post-inflammatory hyperpigmentation were evaluated. RESULTS: In both objective or subjective outcomes, 91.3% (21/23) of the patients showed an excellent or better outcome, while 8.7% (2/23) showed no change. A majority of the patients (73.9%, 17/23) experienced no post-inflammatory hyperpigmentation or had slight post-inflammatory hyperpigmentation which quickly resolved within 1 week. Only one (4.3%) patient had extreme post-inflammatory hyperpigmentation which lasted for over a month. LIMITATIONS: This was a retrospective study without a control group; a comparative study with a control group (patients treated with the laser alone, without vitamin C sonopheresis) is needed to determine the difference in the outcome. CONCLUSION: The use of vitamin C sonophoresis along with NdYAG laser may reduce the incidence of adverse effects in Asian patients. Patients experienced obvious improvement in hyperpigmentation and had lower chances of experiencing extreme or severe post-inflammatory hyperpigmentation.

Glass Microspheres 90Y Selective Internal Radiation Therapy and Chemotherapy as First-Line Treatment of Intrahepatic Cholangiocarcinoma.

PURPOSE OF THE REPORT: Intrahepatic cholangiocarcinoma's incidence is increasing. We studied the efficacy of Y selective internal radiation therapy (SIRT) as first-line treatment, with chemotherapy, and compared with the results of chemotherapy alone. PATIENTS AND METHODS: We retrospectively studied data from patients treated at our institution with glass microspheres SIRT for intrahepatic cholangiocarcinoma as part of first-line treatment in combination with chemotherapy. We compared results with those of similar patients treated in the ABC-02 study (a study in advanced biliary tract cancer that defined the current standard chemotherapy), assessed as not progressing after the first evaluation. We assessed progression-free survival (PFS) and overall survival (OS). RESULTS: Twenty-four patients were treated with SIRT. Chemotherapy was given concomitantly in 10 (42%), as induction before SIRT in 13 (54%) or after SIRT in 1 (4%). Grade 3 adverse events were reported in 1 (4%). Median PFS after SIRT was 10.3 months. Longer PFS was observed when chemotherapy was given concomitantly than when chemotherapy was given before SIRT, with respective median of 20.0 versus 8.8 months (P = 0.001). Median OS after SIRT was not reached. Eleven patients went to surgery (46%). Thirty-three patients in ABC-02 had locally advanced nonextrahepatic cholangiocarcinoma, not progressing after first evaluation. From the start of any treatment, the median PFS was 16.0 months in our cohort versus 11.3 months in ABC-02 (P = 0.25), whereas the median OS was significantly higher in our cohort, not reached versus 17.9 months, respectively (P = 0.026). CONCLUSIONS: Selective internal radiation therapy combined with concomitant chemotherapy seems a promising strategy as first-line treatment for unresectable intrahepatic cholangiocarcinoma.

Cytotoxicity and genotoxicity caused by yttrium oxide nanoparticles in HEK293 cells.

BACKGROUND: The increased use of engineered nanoparticles (NPs) has caused new concerns about the potential exposure to biological systems and the potential risk that these materials may pose on human health. Here, we examined the effects of exposure to different concentrations (0-50 µg/mL) and incubation times (10 hours, 24 hours, or 48 hours) of yttrium oxide (Y2O3) NPs on human embryonic kidney (HEK293) cells. Changes in cellular morphology, cell viability, cell membrane integrity, reactive oxygen species levels, mitochondrial membrane potential, cell death (apoptosis and necrosis), and the DNA damage after NP exposure were compared to the effects seen following incubation with paraquat, a known toxicant. RESULTS: The 24-hour inhibitory concentration 50 (IC50) of Y2O3 NPs (41 ± 5 nm in size) in the HEK293 cells was found to be 108 µg/mL. Incubation with Y2O3 NPs (12.25-50 µg/mL) increased the ratio of Bax/Bcl-2, caspase-3 expression and promoted apoptotic- and necrotic-mediated cell death in both a concentration and a time-dependent manner. Decreases in cell survivability were associated with elevations in cellular reactive oxygen species levels, increased mitochondrial membrane permeability, and evidence of DNA damage, which were consistent with the possibility that mitochondria impairment may play an important role in the cytotoxic response. CONCLUSION: These data demonstrate that the Y2O3 NP exposure is associated with increased cellular apoptosis and necrosis in cultured HEK293 cells.

Improved adhesion of Y-TZP ceramics: a novel approach for surface modification.

The aim of this study was to evaluate the effect of novel surface treatments of Y-TZP ceramics on initial shear bond strengths to resin cement. Eighty-four samples (7 x 6 x 5 mm) were randomly divided into 6 groups (n=14): Group1 (G1), no treatment; Group 2 (G2), air-borne particle abrasion with silica-coated aluminum oxide particles; Group 3 (G3), vitreous application 1 + etching with hydrofluoric acid; Group 4 (G4), vitreous application 1 + tribosilicatization; Group 5 (G5), vitreous application 2 + etching; Group 6 (G6), vitreous application 2 + tribosilicatization. Surface roughness (Ra) evaluation was performed by optical profilometry, scanning electron microscopy, and X-ray spectroscopy. The samples were silanized, and resin cement cylinders (3 x 2 mm) were built on the treated surfaces, light-cured and submitted to shear testing (1 mm/min). The failure mode was evaluated by SEM. Bond strength data were statistically analyzed using 1-way ANOVA and Tukey's test (α=0.05). Bond strength results were significantly affected by surface treatments (P = 0.0001). G5 and G3 presented increased Ra parameters and showed highest bond strength results (17.8 ± 5.5 and 13.3 ± 4.1, respectively). Failure modes were mainly mixed in all groups except for G1. The results confirmed that the approach of coating surface-conditioned Y-TZP with a vitreous material increased the initial shear bond strength to resin cement.

Treatment modification of yttrium-90 radioembolization based on quantitative positron emission tomography/CT imaging.

Treatment activity for yttrium-90 ((90)Y) radioembolization when calculated by using the manufacturer-recommended technique is only partially patient-specific and may result in a subtumoricidal dose in some patients. The authors describe the use of quantitative (90)Y positron emission tomography/computed tomography as a tool to provide patient-specific optimization of treatment activity and evaluate this new method in a patient who previously received traditional (90)Y radioembolization. The modified treatment resulted in a 40-Gy increase in absorbed dose to tumor and complete resolution of disease in the treated area within 3 months.

Thermo and mechanical cycling and veneering method do not influence Y-TZP core/veneer interface bond strength.

OBJECTIVES: The purpose of this study was to evaluate the influence of thermal and mechanical cycling and veneering technique on the shear bond strength of Y-TZP (yttrium oxide partially stabilized tetragonal zirconia polycrystal) core-veneer interfaces. MATERIALS AND METHODS: Cylindrical Y-TZP specimens were veneered either by layering (n=20) or by pressing technique (n=20). A metal ceramic group (CoCr) was used as control (n=20). Ten specimens for each group were thermal and mechanical cycled and then all samples were subjected to shear bond strength in a universal testing machine with a 0.5mm/min crosshead speed. Mean shear bond strength (MPa) was analysed with a 2-way analysis of variance and Tukey's test (p<0.05). Failure mode was determined using stereomicroscopy and scanning electron microscopy (SEM). RESULTS: Thermal and mechanical cycling had no influence on the shear bond strength for all groups. The CoCr group presented the highest bond strength value (p<0.05) (34.72 ± 7.05 MPa). There was no significant difference between Y-TZP veneered by layering (22.46 ± 2.08 MPa) or pressing (23.58 ± 2.1 MPa) technique. Failure modes were predominantly adhesive for CoCr group, and cohesive within veneer for Y-TZP groups. CONCLUSIONS: Thermal and mechanical cycling, as well as the veneering technique does not affect Y-TZP core-veneer bond strength. CLINICAL SIGNIFICANCE: Different methods of veneering Y-TZP restorations would not influence the clinical performance of the core/veneer interfaces.

Urinary monitoring of exposure to yttrium, scandium, and europium in male Wistar rats.

On the assumption that rare earth elements (REEs) are nontoxic, they are being utilized as replacements of toxic heavy metals in novel technological applications. However, REEs are not entirely innocuous, and their impact on health is still uncertain. In the past decade, our laboratory has studied the urinary excretion of REEs in male Wistar rats given chlorides of europium, scandium, and yttrium solutions by one-shot intraperitoneal injection or oral dose. The present paper describes three experiments for the suitability and appropriateness of a method to use urine for biological monitoring of exposure to these REEs. The concentrations of REEs were determined in cumulative urine samples taken at 0-24 h by inductively coupled plasma atomic emission spectroscopy, showing that the urinary excretion of REEs is <2 %. Rare earth elements form colloidal conjugates in the bloodstream, which make high REEs accumulation in the reticuloendothelial system and glomeruli and low urinary excretion. The high sensitivity of inductively coupled plasma-argon emission spectrometry analytical methods, with detection limits of <2 µg/L, makes urine a comprehensive assessment tool that reflects REE exposure. The analytical method and animal experimental model described in this study will be of great importance and encourage further discussion for future studies.

Nano rare-earth oxides induced size-dependent vacuolization: an independent pathway from autophagy.

Four rare earth oxides have been shown to induce autophagy. Interestingly, we often noticed plentiful vacuolization, which was not always involved in this autophagic process. In this study, we investigated three other rare-earth elements, including Yttrium (Y), Ytterbium (Yb), and Lanthanum (La). Autophagic effect could be induced by all of them but only Y(2)O(3) and Yb(2)O(3) could cause massive vacuolization. Y(2)O(3) and Yb(2)O(3) treated by sonication or centrifugation to reduce particle size were used to test vacuolization level in HeLa cell lines. The results showed that rare earth oxides-induced vacuolization is size-dependent and differs from autophagic pathway. To further clarify the characteristics of this autophagic process, we used MEF Atg-5 (autophagy associated gene 5) knockout cell line, and the result showed that the autophagic process induced by rare earth oxides is Atg-5-dependent and the observed vacuolization was independent from autophagy. Similar results could also be observed in our tests on 3-methyladenine(3-MA), a well-known autophagy inhibitor. In conclusion, for the first time, we clarified the relationship between massive vacuolization and autophagic process induced by rare earth oxides and pointed out the size effect of rare earth oxides on the formation of vacuoles, which give clues to further investigation on the mechanisms underlying their biological effects.

Radioembolization with use of yttrium-90 resin microspheres in patients with hepatocellular carcinoma and portal vein thrombosis.

PURPOSE: Intraarterial delivery of yttrium-90 ((90)Y)-bound microspheres (ie, radioembolization) is a promising treatment for hepatocellular carcinoma (HCC). An early concern was the "embolic" nature of the microspheres, and their potential to reduce hepatic arterial blood flow in patients with compromised portal blood flow secondary to portal vein thrombosis/occlusion (PVT). In this situation, the risk of liver failure could be enhanced, particularly in patients with cirrhosis who have increased hepatic arterial blood flow. This retrospective analysis was undertaken to assess the safety and clinical benefits of radioembolization with (90)Y resin microspheres in HCC with branch or main PVT. MATERIALS AND METHODS: A total of 25 patients presenting with unresectable HCC and compromised portal flow received segmental, lobar, or whole-liver infusion of (90)Y resin microspheres. For the analysis of tumor response, changes in target lesions, appearance of new lesions, and changes in portal vein thrombus were studied. Controlled disease was defined by absence of progression in all these components. RESULTS: Globally, controlled disease was achieved in 66.7% of patients at 2 months and 50% of patients at 6 months. No significant changes were observed in liver-related toxicities according to Common Toxicity Criteria (version 3.0) at 1 and 2 months after treatment. Median survival time was 10 months (95% CI, 6.6-13.3 months). CONCLUSIONS: Radioembolization of unresectable HCC and branch or main PVT with (90)Y resin microspheres was associated with minimal toxicity and a favorable median survival time. Further prospective studies are warranted to validate the findings in this clinically challenging patient population.