Genotoxic and ecotoxic assessments of widely used nanoparticles, cerium dioxide (CeO(2)), silicon dioxide (SiO(2)) and titanium dioxide (TiO(2)), were conducted on two aquatic sentinel species, the freshwater crustacean Daphnia magna and the larva of the aquatic midge Chironomus riparius. CeO(2) may have genotoxic effects on D. magna and C. riparius, given that the DNA strand breaks increased in both species when exposed to this nanoparticle; whereas, neither exposure to SiO(2) nor TiO(2) had a genotoxic effect on either species. A statistically significant correlation was observed between DNA damage and mortality in the CeO(2)-exposed C. riparius, which suggests that CeO(2)-induced DNA damage might provoke higher-level consequences. SiO(2) did not seem to affect the DNA integrity; whereas, the mortality of both the SiO(2)-exposed D. magna and C. riparius increased. The TiO(2) nanoparticle did not lead to significant alterations in geno- or ecotoxic parameters of both species. Overall, these results suggest that CeO(2) nanoparticles may be genotoxic toward aquatic organisms, which may contribute to the knowledge relating to the aquatic toxicity of the most widely used nanomaterials on aquatic ecosystems, for which little data are available.

A 62-year-old man presented with bilateral diffuse uveal melanocytic proliferations (BDUMP) and painful flexor contractures of the fingers of both hands. All these features were considered paraneoplastic but extensive and repeated investigations revealed no underlying malignancy. Oral steroids and orbital radiotherapy were ineffective. The diagnosis was confirmed by trans-scleral biopsy of the right choroid. Rapidly progressive cataracts were treated by phacoemulsification. Severe exudative retinal detachment with rubeosis and neovascular glaucoma in the left eye were treated successfully by partial choroidectomy. Fifteen months after presentation, investigations detected a 22 mm, poorly differentiated adenocarcinoma, which was resected without complication. The ocular tumours in both eyes regressed, without improvement in vision of Light Perception, and the palmar fasciitis also improved. The patient remained free of tumour recurrence until sudden death from myocardial infarction five years after he first presented.

Infectious laryngotracheitis (ILT) is a highly contagious acute respiratory disease of chickens caused by infectious laryngotracheitis virus (ILTV). The disease is controlled mainly through biosecurity and vaccination with live attenuated strains of ILTV and vectored vaccines based on turkey herpesvirus (HVT) and fowlpox virus (FPV). The current live attenuated vaccines (chicken embryo origin [CEO] and tissue culture origin [TCO]), although effective, can regain virulence, whereas HVT- and FPV-vectored ILTV vaccines are less efficacious than live attenuated vaccines. Therefore, there is a pressing need to develop safer and more efficacious ILTV vaccines. In the present study, we generated Newcastle disease virus (NDV) recombinants, based on the LaSota vaccine strain, expressing glycoproteins B (gB) and D (gD) of ILTV using reverse genetics technology. These recombinant viruses, rLS/ILTV-gB and rLS/ILTV-gD, were slightly attenuated in vivo yet retained growth dynamics, stability, and virus titers in vitro that were similar to those of the parental LaSota virus. Expression of ILTV gB and gD proteins in the recombinant virus-infected cells was detected by immunofluorescence assay. Vaccination of specific-pathogen-free chickens with these recombinant viruses conferred significant protection against virulent ILTV and velogenic NDV challenges. Immunization of commercial broilers with rLS/ILTV-gB provided a level of protection against clinical disease similar to that provided by the live attenuated commercial vaccines, with no decrease in body weight gains. The results of the study suggested that the rLS/ILTV-gB and -gD viruses are safe, stable, and effective bivalent vaccines that can be mass administered via aerosol or drinking water to large chicken populations.

OBJECTIVE

This paper describes the development and evaluation of novel bivalent vaccines against chicken infectious laryngotracheitis (ILT) and Newcastle disease (ND), two of the most economically important infectious diseases of poultry. The current commercial ILT vaccines are either not safe or less effective. Therefore, there is a pressing need to develop safer and more efficacious ILT vaccines. In the present study, we generated Newcastle disease virus (NDV) recombinants expressing glycoproteins B (gB) and D (gD) of infectious laryngotracheitis virus (ILTV) using reverse genetics technology. These recombinant viruses were safe, stable, and immunogenic and replicated efficiently in birds. Vaccination of chickens with these recombinant viruses conferred complete protection against ILTV and NDV challenge. These novel bivalent vaccines can be mass administered via aerosol or drinking water to large chicken populations at low cost, which will have a direct impact on poultry health, fitness, and performance.

Interviewed by Ellen Clarke, Commissioning Editor, Future Science Group. Robert Coffin is co-founder and CEO of Replimune. Previously he was Founder and CTO of BioVex Inc, a spin out from his research group at University College London in 1999. He was the inventor of all BioVex products including OncoVEXGM-CSF (talimogene laherparepvec; T-VEC; Imlygic) and oversaw all research and clinical development including bringing T-VEC through to two pivotal Phase 3 studies in melanoma and head and neck cancer. BioVex was acquired by Amgen in 2011 where he was VP Global Development until 2013. T-VEC was approved by the FDA for use in advanced melanoma in October 2015, the first oncolytic therapy or gene therapy to be approved in USA. He was awarded a PhD in virology from Imperial College London prior to his move to University College London in 1991.

BACKGROUND

The central idea of process-based organization design is that organizing a firm around core business processes leads to cost reductions and quality improvements.

OBJECTIVE

We investigated theoretically and empirically whether the implementation of a process-based organization design is advisable in hospitals.

METHODS

The data came from a database compiled by the Statistical Office of the German federal state of Rheinland-Pfalz and from a written questionnaire, which was sent to the chief executive officers (CEOs) of all 92 hospitals in this federal state. We used data envelopment analysis (DEA) to measure hospital efficiency, and factor analysis and regression analysis to test our hypothesis.

RESULTS

Our principal finding is that a high degree of process-based organization has a moderate but significant positive effect on the efficiency of hospitals.

CONCLUSIONS

The main implication is that hospitals should implement a process-based organization to improve their efficiency. However, to actually achieve positive effects on efficiency, it is of paramount importance to observe some implementation rules, in particular to mobilize physician participation and to create an adequate organizational culture.

The catalytic performance of ceria nanoparticles is generally attributed to active sites on the particle surface. The creation of oxygen vacancies and thus nonstoichiometric CeO(2-δ) has been proposed to result in Ce(3+) sites with unpaired f electrons which can be oxidized to spinless Ce(4+) ions during catalytic reactions. We monitored the Ce electronic structure during the synthesis and catalase mimetic reaction of colloidal ceria nanoparticles under in situ conditions. By means of high-energy resolution hard X-ray spectroscopy, we directly probed the Ce 4f and 5d orbitals. We observe pronounced changes of the Ce 5d bands upon reduction of the particle size and during the catalytic reaction. The Ce 4f orbitals, however, remain unchanged, and we do not observe any significant number of spin-unpaired Ce(3+) sites even for catalytically active small (3 nm) particles with large surface to bulk ratio. This confirms strong orbital mixing between Ce and O, and the Ce spin state is conserved during the reaction. The particles show an increase of the interatomic distances between Ce and O during the catalytic decomposition of hydrogen peroxide. The redox partner is therefore not a local Ce(3+) site, but the electron density that is received and released during the catalytic reaction is delocalized over the atoms of the nanoparticle. This invokes the picture of an electron sponge.

OBJECTIVE

To review epidemiological features of orbital tumours in Japan.

METHODS

Retrospective, observational case series and systematic review. A total of 104 patients with orbital tumours collected at the authors' institution during 1983-2002 were assessed. In addition, 1379 cases from a large series of orbital tumours diagnosed by histopathological analysis that were previously published in Japanese ophthalmological journals from 1980 to 2004 were analysed.

RESULTS

After combining the current data with the previously published cases, there were a total of 1483 lesions with 47% classified as primary, 30% as secondary and 22% as inflammatory. The most common primary tumour was malignant lymphoma (12%) followed by pleomorphic adenoma (7%). Carcinomas from the lung, breast and thyroid were found to predominate among orbital metastases. Inflammatory pseudotumour had the highest lesion frequency (18%).

CONCLUSIONS

Malignant lymphoma by far was found to have the most dramatic increases within the recent reported series. Pleomorphic adenomas in Japan were found to be much more common compared with that reported for American and European studies.

One of the recent trends in the food industry is application of natural antioxidant/antimicrobial agents. In this study, essential oil of clove buds was extracted and encapsulated in chitosan nanoparticles using a two-step technique of emulsion-ionic gelation. A good retention rate (55.8-73.4 %) of clove essential oil (CEO) loaded in chitosan nanoparticles was confirmed. Also, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analyses revealed the success of CEO encapsulation. Scanning electron microscopy (SEM) images illustrated regular distribution and spherical shape of nanoparticles with a size range of 223-444 nm. The antioxidant activity of CEO-loaded chitosan nanoparticles was higher than free CEO. Similarly, CEO-loaded chitosan nanoparticles had a high antibacterial activity against L. monocytogenes and S. aureus (inhibition halo diameter of 4.80-4.78 cm). This technique could improve the efficiency of CEO in food products and a delivery system for novel applications such as active packaging.

Cerium oxide nanoparticles (CeNPs) exhibit antioxidant properties both in vitro and in vivo. This is due to the self-regeneration of their surface, which is based on redox-cycling between 3+ and 4+ states for cerium, in response to their immediate environment. Additionally, oxygen vacancies in the lattice structure allow for alternating between <em>CeO</em>₂ and <em>CeO</em>2-x during redox reactions. Research to identify and characterize the biomedical applications of CeNPs has been heavily focused on investigating their use in treating diseases that are characterized by higher levels of reactive oxygen species (ROS). Although the bio-mimetic activities of CeNPs have been extensively studied in vitro, in vivo interactions and associated protein corona formation are not well understood. This review describes: (1) the methods of synthesis for CeNPs, including the recent green synthesis methods that offer enhanced biocompatibility and a need for establishing a reference CeNP material for consistency across studies; (2) their enzyme-mimetic activities, with a focus on their antioxidant activities; and, (3) recent experimental evidence that demonstrates their ROS scavenging abilities and their potential use in personalized medicine.

Engineered nanomaterials, defined as having at least one dimension smaller than 100 nm, have revolutionized many technology sectors ranging from therapeutics and diagnostics to environmental monitoring and remediation. This has resulted in a rapid increase in their manufacture over the past few years, accompanied by an increased human exposure potential. However, understanding of the interactions of nanomaterials with biological systems is still rudimentary. We have described that an environmentally and medically relevant nano metal (cerium dioxide) can affect primary human monocyte viability and interact with programmed cell death pathways leading to apoptosis and autophagic cell death. Cerium dioxide nanoparticles (CeO 2 NPs)-induced autophagy acts as a prodeath mechanism and leads to increased cytotoxicity of human monocytes. A better understanding of the implication and biological significance of CeO 2 NPs-induced autophagy and apoptosis will help us understand the risks associated with its uses and develop safer nanomedicine.

In the first half of the third century B.C, two Greeks, Herophilus of Chalcedon and his younger contemporary Erasistratus of Ceos, became the first and last ancient scientists to perform systematic dissections of human cadavers. In all probability, they also conducted vivisections of condemned criminals. Their anatomical and physiological discoveries were extraordinary. The uniqueness of these events presents an intriguing historical puzzle. Animals had been dissected by Aristotle in the preceding century (and partly dissected by other Greeks in earlier centuries), and, later, Galen (second century A.D.) and others again systematically dissected numerous animals. But no ancient scientists ever seem to have resumed systematic human dissection. This paper explores, first, the cultural factors--including traditional Greek attitudes to the corpse and to the skin, also as manifested in Greek sacred laws--that may have prevented systematic human dissection during almost all of Greek antiquity, from the Pre-Socratic philosopher-scientists of the sixth and fifth centuries B.C. to distinguished Greek physicians of the later Roman Empire. Second, the exceptional constellation of cultural, political, and social circumstances in early Alexandria that might have emboldened Herophilus to overcome the pressures of cultural traditions and to initiate systematic human dissection, is analyzed. Finally, the paper explores possible reasons for the mysteriously abrupt disappearance of systematic human dissection from Greek science after the death of Erasistratus and Herophilus.

The aim of this study was to compare the biological response of a sophisticated in vitro 3D co-culture model of the epithelial airway barrier to a co-exposure of CeO(2) NPs and diesel exhaust using a realistic air-liquid exposure system. Independent of the individual effects of either diesel exhaust or CeO(2) NPs investigation observed that a combined exposure of CeO(2) NPs and diesel exhaust did not cause a significant cytotoxic effect or alter cellular morphology after exposure to diesel exhaust for 2h at 20μg/ml (low dose) or for 6h at 60μg/ml (high dose), and a subsequent 6h exposure to an aerosolized solution of CeO(2) NPs at the same doses. A significant loss in the reduced intracellular glutathione level was recorded, although a significant increase in the oxidative marker HMOX-1 was found after exposure to a low and high dose respectively. Both the gene expression and protein release of tumour necrosis factor-α were significantly elevated after a high dose exposure only. In conclusion, CeO(2) NPs, in combination with diesel exhaust, can significantly interfere with the cell machinery, indicating a specific, potentially adverse role of CeO(2) NPs in regards to the biological response of diesel exhaust exposure.

Meiosis activating sterol, produced directly by lanosterol 14-alpha-demethylase (CYP51) during cholesterol biosynthesis, has been shown to promote the initiation of oocyte meiosis. However, the physiological significance of CYP51 action on oocyte meiosis in response to gonadotrophins' induction remained to be further explored. Herein, we analyzed the role of CYP51 in gonadotrophin-induced in vitro oocyte maturation via RNA interference (RNAi). We showed that although both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) significantly induced meiotic resumption in follicle-enclosed oocytes (FEOs), the effect of LH on oocyte meiosis resumption in FEOs was weaker than FSH. Moreover, both FSH and LH were able to upregulate CYP51 expression in cultured follicular granulosa cells when examined at 8 h or 12 h posttreatments, respectively. Interestingly, whereas knockdown of CYP51 expression via small interference RNA (siRNA) moderately blocked (23% reduction at 24 h) FSH-induced oocyte maturation [43% germinal vesicle breakdown (GVBD) rate in RNAi vs. 66% in control, P < 0.05] in FEOs, similar treatments showed no apparent effects on LH-induced FEO meiotic maturation (58% GVBD rate in RNAi vs. 63% in control, P>> 0.05). Moreover, the results in a cumulus-enclosed oocytes (CEOs) model showed that approximately 30% of FSH-induced CEOs' meiotic resumption was blocked upon CYP51 knockdown by siRNAs. These findings suggest that FSH, partially at least, employs CYP51, and therefore the MAS pathway, to initiate oocyte meiosis.

Several chemical signals synthesized in the ovary, including neurotransmitters, have been proposed to serve as regulators of folliculogenesis, however, their mechanisms of action have not been completely elucidated. Here, electrophysiological and molecular biology techniques were used to study responses generated via purinergic stimulation in cultured mouse cumulus cell-enclosed oocytes (CEOs). Application of extracellular ATP elicited depolarizing responses in CEOs. Using the voltage clamp technique by impaling oocytes with two microelectrodes, we determined that these responses were mainly due to activation of two distinct ionic currents. The first corresponded to the opening of Ca2+-dependent Cl- channels (I(Cl(Ca))) and the second to the opening of Ca2+-independent channels that are permeable to Na+ (I(c+)). The potency order for different nucleotides (50 micro M) was UTP>> ATP>> 2meS-ATP>> ADP, and alpha,betame-ATP and adenosine were found to be inactive. Suramin (100 micro M) blocked the response elicited by ATP or UTP. In addition, voltage dependent K+ currents activated by depolarization of CEOs were characterized. All CEO ionic currents recorded from the oocyte were completely inhibited by octanol (1 mM), a gap junction blocker. Thus, purinergic responses and K+ currents originate mainly in the membrane of cumulus cells. Transcripts of the purinergic receptor P2Y2 subtype were amplified by polymerase chain reaction from the cDNA of granulosa cells or cumulus cells. This study shows that P2Y2 receptors are expressed in CEOs, and that their stimulation opens at least two different types of ion channels. Both the ion channels and the receptors seemed to be located in the cumulus cells, which transmit their corresponding electrical signals to the oocyte via gap junction channels.

Hospital governing boards assume an important role in improving delivery of quality care in the hospital. More knowledge about the prevalence and impact of particular board activities can help them perform this role more effectively. This study draws from a survey of hospital and system leaders (presidents/chief executive officers [CEOs]) that was conducted in the first six months of 2006 with a total of 562 respondents. The survey contained 27 questions on various aspects of board engagement in quality. More than 80 percent of the responding CEOs indicated that their governing boards establish strategic goals for quality improvement, use quality dashboards to track performance, and follow up on corrective actions related to adverse events. The adoption of other practices was reported less frequently. Only 61 percent of the respondents indicated that their governing boards have a quality committee. The existence of a board quality committee was associated with higher likelihoods of adopting various oversight practices and lower mortality rates for six common medical conditions measured by the Agency for Healthcare Research and Quality's Inpatient Quality Indicators and the State Inpatient Databases. Hospital governing boards appear to be actively engaged in quality oversight, particularly through use of internal data and national benchmarks to monitor the quality performance of their organizations. Having a board quality committee can significantly enhance the board's oversight function. Other potentially useful activities-such as board involvement in setting the agenda for the discussion on quality, inclusion of the quality measures in the CEO's performance evaluation, and improvement of quality literacy of board members-are currently performed infrequently.

The CeO₂ NPs are increasingly used in industry but the environmental release of these NPs and their subsequent behavior and biological effects are currently unclear. This study evaluates for the first time the effects of CeO₂ NPs on the survival and the swimming performance of two cladoceran species, Daphnia similis and Daphnia pulex after 1, 10 and 100 mg.L⁻¹ CeO₂ exposures for 48 h. Acute toxicity bioassays were performed to determine EC₅₀ of exposed daphnids. Video-recorded swimming behavior of both daphnids was used to measure swimming speeds after various exposures to aggregated CeO₂ NPs. The acute ecotoxicity showed that D. similis is 350 times more sensitive to CeO₂ NPs than D. pulex, showing 48-h EC₅₀ of 0.26 mg.L⁻¹ and 91.79 mg.L⁻¹, respectively. Both species interacted with CeO₂ NPs (adsorption), but much more strongly in the case of D. similis. Swimming velocities (SV) were differently and significantly affected by CeO₂ NPs for both species. A 48-h exposure to 1 mg.L⁻¹ induced a decrease of 30% and 40% of the SV in D. pulex and D. similis, respectively. However at higher concentrations, the SV of D. similis was more impacted (60% off for 10 mg.L⁻¹ and 100 mg.L⁻¹) than the one of D. pulex. These interspecific toxic effects of CeO₂ NPs are explained by morphological variations such as the presence of reliefs on the cuticle and a longer distal spine in D. similis acting as traps for the CeO₂ aggregates. In addition, D. similis has a mean SV double that of D. pulex and thus initially collides with twice more NPs aggregates. The ecotoxicological consequences on the behavior and physiology of a CeO₂ NPs exposure in daphnids are discussed.

Organizational-level variables that are hypothesized to influence the level of smoking policy restrictions and the prevalence of smoking control activities were tested in a sample of 1 14 worksites that participated in the Working Well Trial, a national trial of worksite health promotion. Predictors related to more restrictive policies included smaller size, larger percentage of white-collar workers, larger number of complaints about environmental tobacco smoke, less complexity, more formalization, and having a CEO who valued health and employees' well-being. The number of smoking control activities offered in a worksite was predicted by having a larger blue-collar workforce, a higher percentage of female employees, higher levels of workforce stability, and a CEO who valued health and employees' well-being. Efforts to identify predictors of companies' adoption and implementation of workplace-based policies and interventions are an important part of tobacco control efforts and will enhance future intervention and research efforts.

BACKGROUND

The age-related eye disease study suggested that taking zinc and anti-oxidants supplements could reduce the progression of age-related macular degeneration (AMD). In Australia, the available supplement is Macu-Vision. The study aimed to assess the awareness of and compliance with taking this supplement and the public health implication.

METHODS

The fundus photograph database of patients aged 55 years and older at the ophthalmology department of a public teaching hospital in Adelaide, Australia was reviewed. In total, 125 patients with category 3 and 4 AMD were identified. A total of 100 patients participated in this cross-sectional study.

RESULTS

In total, 53% of participants were aware of the availability of the formulae available in Australia, 38% were taking the supplement and only 1% were taking the correct dose. Of those taking the supplement 95% (36/38) were taking half the recommended dosage. Among those who were aware of the supplement but not taking it, cost was the most common reason (31%). Another 31% were not taking it because of actual side-effects experienced, fear of potential side-effect and/or fear of interaction with other medications. There was no predictive factor for failing to take the formulae available in Australia among age, sex, smoking status, living arrangement and category of AMD.

CONCLUSIONS

Clinicians need to emphasize that the recommended dosage is twice that on the supplement label. If the trend demonstrated here of underutilizing the formulae available in Australia among public hospital patients continues, it is unlikely to have any major public health impact in similar settings in Australia.

The use of a heterogeneous Lewis acid catalyst, which is insoluble and easily separable during the reaction, is a promising option for hydrolysis reactions from both environmental and practical viewpoints. In this study, ceria showed excellent catalytic activity in the hydrolysis of 4-methyl-1,3-dioxane to 1,3-butanediol in 95% yield and in the one-pot synthesis of 1,3-butanediol from propylene and formaldehyde via Prins condensation and hydrolysis reactions in an overall yield of 60%. In-depth investigations revealed that ceria is a water-tolerant Lewis acid catalyst, which has seldom been reported previously. The ceria catalysts showed rather unusual high activity in hydrolysis, with a turnover number (TON) of 260, which is rather high for bulk oxide catalysts, whose TONs are usually less than 100. Our conclusion that ceria functions as a Lewis acid catalyst in hydrolysis reactions is firmly supported by thorough characterizations with IR and Raman spectroscopy, acidity measurements with IR and (31)P magic-angle-spinning NMR spectroscopy, Na(+)/H(+) exchange tests, analyses using the in situ active-site capping method, and isotope-labeling studies. A relationship between surface vacancy sites and catalytic activity has been established. CeO(2)(111) has been confirmed to be the catalytically active crystalline facet for hydrolysis. Water has been found to be associatively adsorbed on oxygen vacancy sites with medium strength, which does not lead to water dissociation to form stable hydroxides. This explains why the ceria catalyst is water-tolerant.

Because genetically modified crops are developing widely in the world while nanoparticles (NPs) are being synthesized and applied in various fields, they will have many opportunities for interactions in the future. The effects of NPs on genetically modified crops therefore require investigation. In the present study, CeO2 NPs were revealed to have toxic effects on root biomass of Bt 29317 at 100 and 500 mg L(-1), but had no toxic effects on Jihe 321. Besides, we also studied the effects of CeO2 NPs on nutrient element uptake in transgenic cotton, and found that contents of most nutrient elements (Fe, Ca, Mg, Zn and Na) in roots of Bt 29317 were affected at lower NP concentrations (100 mg L(-1)) compared with Jihe 321. In addition, ICP-MS analysis revealed that CeO2 NPs were more heavily adsorbed by roots of Bt 29317 than Jihe 321, whereas fewer CeO2 NPs were transported from roots to shoots of Bt 29317 than its non-transgenic counterpart. These data confirm that Bt 29317 is more sensitive to CeO2 NPs than its parental non-transgenic cotton, indicating that nanomaterials are potentially more detrimental to transgenic plants than conventional ones.

BACKGROUND

Nanoparticulate barium sulfate has potential novel applications and wide use in the polymer and paint industries. A short-term inhalation study on barium sulfate nanoparticles (BaSO₄ NPs) was previously published [Part Fibre Toxicol 11:16, 2014]. We performed comprehensive biokinetic studies of ¹³¹BaSO₄ NPs administered via different routes and of acute and subchronic pulmonary responses to instilled or inhaled BaSO₄ in rats.

METHODS

We compared the tissue distribution of ¹³¹Ba over 28 days after intratracheal (IT) instillation, and over 7 days after gavage and intravenous (IV) injection of ¹³¹BaSO₄. Rats were exposed to 50 mg/m³ BaSO₄ aerosol for 4 or 13 weeks (6 h/day, 5 consecutive days/week), and then gross and histopathologic, blood and bronchoalveolar lavage (BAL) fluid analyses were performed. BAL fluid from instilled rats was also analyzed.

RESULTS

Inhaled BaSO₄ NPs showed no toxicity after 4-week exposure, but a slight neutrophil increase in BAL after 13-week exposure was observed. Lung burden of inhaled BaSO₄ NPs after 4-week exposure (0.84 ± 0.18 mg/lung) decreased by 95% over 34 days. Instilled BaSO₄ NPs caused dose-dependent inflammatory responses in the lungs. Instilled BaSO₄ NPs (0.28 mg/lung) was cleared with a half-life of ≈ 9.6 days. Translocated ¹³¹Ba from the lungs was predominantly found in the bone (29%). Only 0.15% of gavaged dose was detected in all organs at 7 days. IV-injected ¹³¹BaSO₄ NPs were predominantly localized in the liver, spleen, lungs and bone at 2 hours, but redistributed from the liver to bone over time. Fecal excretion was the dominant elimination pathway for all three routes of exposure.

CONCLUSIONS

Pulmonary exposure to instilled BaSO₄ NPs caused dose-dependent lung injury and inflammation. Four-week and 13-week inhalation exposures to a high concentration (50 mg/m³) of BaSO₄ NPs elicited minimal pulmonary response and no systemic effects. Instilled and inhaled BaSO₄ NPs were cleared quickly yet resulted in higher tissue retention than when ingested. Particle dissolution is a likely mechanism. Injected BaSO₄ NPs localized in the reticuloendothelial organs and redistributed to the bone over time. BaSO₄ NP exhibited lower toxicity and biopersistence in the lungs compared to other poorly soluble NPs such as CeO₂ and TiO₂.

BACKGROUND

In this study, we compared the relative ability of FSH (100 mIU/ml), epidermal growth factor (EGF) (10 ng/ml), and follicular-fluid meiosis-activating sterol (FF-MAS, 10 micromol/l) to induce meiotic resumption and polar body I (PBI) extrusion in mouse oocytes.

METHODS

Cumulus-enclosed oocytes (CEO) were co-incubated with meiosis-arresting agents, including 4 mmol/l hypoxanthine (Hx), 0.3 mmol/l dibutyryl cAMP (dbcAMP), and 8.5 micromol/l cilostamide, a selective inhibitor of the oocyte-specific phosphodiesterase 3 (PDE 3).

RESULTS

In Hx-treated oocytes, FSH, EGF and FF-MAS induced meiosis resumption at very high rates, but only FSH and EGF also promoted PBI extrusion with high frequency. In experiments conducted in the presence of dbcAMP, FF-MAS was unable to promote an increase in germinal vesicle breakdown (GVBD) rate, whereas FSH and EGF generated a response similar to the Hx groups. Neither FSH, EGF nor FF-MAS caused any change in the meiotic status of CEO when meiotic arrest at the germinal vesicle (GV) stage was maintained by cilostamide. In the presence of Hx, naked oocytes (NkO) co-cultured with their cumulus cells were able to respond to the GVBD-inducing effect of FSH and EGF by resuming meiosis at high rate.

CONCLUSIONS

Collectively, these results indicate that: (i) a signal triggered in cumulus cells by either FSH or EGF, but not necessarily coincident with FF-MAS, may contribute to meiotic maturation, supporting GVBD and extrusion of PBI; (ii) the transmission of this signal can occur in a paracrine fashion, at least with reference to the breakdown of the GV. It also appears that concomitant regulation of intra-oocyte cAMP degradation is a prerequisite for meiosis resumption.

A novel Mn-Ce oxide adsorbent with high sorption capacity for fluoride was prepared via co-precipitation method in this study, and the granular adsorbent was successfully prepared by calcining the mixture of the Mn-Ce powder and pseudo-boehmite. High-resolution transmission electron microscopy (TEM) image showed that the Mn-Ce adsorbent consisted of about 4.5 nm crystals, and X-ray diffraction (XRD) analysis indicated the formation of solid solution by Mn species entering CeO(2) lattices. The surface hydroxyl group density on the Mn-Ce adsorbent was determined to be as high as 15.3 mmol g(-1), mainly responsible for its high sorption capacity for fluoride. Sorption isotherms showed that the sorption capacities of fluoride on the powdered and granular adsorbent were 79.5 and 45.5 mg g(-1) respectively at the equilibrium fluoride concentration of 1 mg L(-1), much higher than all reported adsorbents. Additionally, the adsorption was fast within the initial 1 h. Fourier transform infrared (FTIR) and X-ray photoelectron spectroscopy (XPS) analysis revealed that the hydroxyl groups on the adsorbent surface were involved in the sorption of fluoride. Both anion exchange and electrostatic interaction were involved in the sorption of fluoride on the Mn-Ce oxide adsorbent.

Recently, cerium oxide nanoparticles (CeO2 NPs) has been reported for multi-enzyme mimetic activities like that of superoxide dismutase and catalase. Here, we report glutathione (GSH) replenishing response by CeO2 NPs in human breast (MCF-7) and fibrosarcoma (HT-1080) cells. CeO2 NPs were found to be mostly cuboidal in shape with average diameter of 25 nm. Effects on cell viability, reactive oxygen species (ROS) generation, and mitochondrial outer membrane potential (MOMP) suggested CeO2 NPs to be reasonably non-cytotoxic. Data on membrane damage and lipid peroxidation correlated well with the cell viability results suggesting NPs of CeO2 to be biocompatible. Interestingly, CeO2 NPs significantly increased intracellular GSH in cells challenged with oxidants. Replenishment of depleted GSH in oxidatively challenged cells was comparable with the GSH restoring potential of known antioxidant N-acetyl cysteine (NAC), a precursor of GSH. Like NAC, CeO2 NPs significantly replenished depleted GSH in both cell types challenged with hydrogen peroxide (H2O2) and zinc oxide (ZnO) NPs. Moreover, CeO2 NPs treated cells were significantly protected from cytotoxicity caused by H2O2 and ZnO NPs. Our findings, therefore, suggest CeO2 NPs as a potential antioxidant rather than a toxic material.