Pyrolysis of High-Ash Natural Microalgae from Water Blooms: Effects of Acid Pretreatment.

Natural microalgae (NA, cyanobacteria) collected from Taihu Lake (Jiangsu, China) were used for biofuel production through pyrolysis. The microalgae were de-ashed via pretreatment with deionized water and hydrochloric acid, and the samples obtained were noted as 0 M, 0.1 M, 1 M, 2 M, 4 M, 6 M, 8 M, respectively, according to the concentration of hydrochloric acid used in the pretreatment. Pyrolysis experiments were carried out at 500 °C for 2 h. The products were examined by various techniques to identify the influence of the ash on the pyrolysis behavior. The results showed that the ash inhibited the thermal transformation of microalgae. The 2 mol/L hydrochloric acid performed the best in removing ash and the liquid yield increased from 34.4% (NA) to 40.5% (2 M). Metal-oxides (mainly CaO, MgO, Al2O3) in ash promoted the reaction of hexadecanoic acid and NH3 to produce more hexadecanamide, which was further dehydrated to hexadecanenitrile. After acid pretreatment, significant improvement in the selectivity of hexadecanoic acid was observed, ranging from 22.4% (NA) to 58.8% (4 M). The hydrocarbon compounds in the liquid product increased from 12.90% (NA) to 26.67% (2 M). Furthermore, the acid pretreatment enhanced the content of C9-C16 compounds and the HHV values of bio-oil. For natural microalgae, the de-ashing pretreatment before pyrolysis was essential for improving the biocrude yield and quality, as well as the biomass conversion efficiency.

Biodistribution, cardiac and neurobehavioral assessments, and neurotransmitter quantification in juvenile rats following oral administration of aluminum oxide nanoparticles.

Little is known about the uptake, biodistribution, and biological responses of nanoparticles (NPs) and their toxicity in developing animals. Here, male and female juvenile Sprague-Dawley rats received four consecutive daily doses of 10 mg/kg Al2 O3 NP (diameter: 24 nm [transmission electron microscope], hydrodynamic diameter: 148 nm) or vehicle control (water) by gavage between postnatal days (PNDs) 17-20. Basic neurobehavioral and cardiac assessments were performed on PND 20. Animals were sacrificed on PND 21, and selected tissues were collected, weighed, and processed for histopathology or neurotransmitter analysis. The biodistribution of Al2 O3 NP in tissue sections of the intestine, liver, spleen, kidney, and lymph nodes were evaluated using enhanced dark-field microscopy (EDM) and hyperspectral imaging (HSI). Liver-to-body weight ratio was significantly increased for male pups administered Al2 O3 NP compared with control. HSI suggested that Al2 O3 NP was more abundant in the duodenum and ileum tissue of the female pups compared with the male pups, whereas the abundance of NP was similar for males and females in the other tissues. The abundance of NP was higher in the liver compared with spleen, lymph nodes, and kidney. Homovanillic acid and norepinephrine concentrations in brain were significantly decreased following Al2 O3 NP administration in female and male pups, whereas 5-hydroxyindoleacetic acid was significantly increased in male pups. EDM/HSI indicates intestinal uptake of Al2 O3 NP following oral administration. Al2 O3 NP altered neurotransmitter/metabolite concentrations in juvenile rats' brain tissues. Together, these data suggest that orally administered Al2 O3 NP interferes with the brain biochemistry in both female and male pups.

Effect of low-dose exposure of aluminium oxide nanoparticles in Swiss albino mice: Histopathological changes and oxidative damage.

Rapid growth in the use of aluminium oxide nanoparticles (Al2O3 NPs) in various fields such as medicine, pharmacy, cosmetic industries, and engineering creates concerns since the literature is replete with data regarding their toxicity in living organisms. The objective of the present study was to demonstrate the potential toxicological manifestations of repeated exposure to Al2O3 NP at low doses in vivo. In the present study, Al2O3 NP was orally administered at 15, 30 or 60 mg kg-1 body weight for 5 days to Swiss albino male mice. A battery of well-defined assays was undertaken to evaluate aluminium (Al) bioaccumulation, haematological and histological changes, oxidative damage and genotoxicity. Physico-chemical characterisation demonstrated increases in hydrodynamic diameter along the concentration gradient of Al2O3 NP dispersed in MilliQ water. Brain, liver, spleen, kidney and testes showed high Al retention levels. Histopathological lesions were prominent in the brain and liver. Al2O3 NP treatment increased levels of lipid peroxidation and decreased glutathione content in the test organs at all dose levels. The enzyme activities of catalase and superoxide dismutase were also significantly altered. DNA damage quantified using the comet assay was markedly increased in all the soft organs studied. Anatomical abnormalities, redox imbalance and DNA damage were positively correlated with Al retention in the respective organs. Size, zeta potential and colloidal state might have contributed to the bio-physico-chemical interactions of the NPs in vivo and were responsible for the non-linear dose response. The overall data indicate that Al2O3 NP exposure may result in adverse health consequences, inclusive of but not limited to disturbed redox homeostasis, hepatocellular toxicity, neurodegeneration and DNA damage.

An Alumina Ceramic Total Talar Prosthesis for Avascular Necrosis of the Talus.

Avascular necrosis tends to occur in the talus because of poor blood supply caused by the extended coverage to the articular cartilage on its surface. Treatment is conservative in the earlier stage of this disease; however, surgical treatment is usually indicated in the advanced stage. Nonunion, leg length discrepancy, or hindfoot instability may occur in patients treated with ankle or tibio-talo-calcaneal fusion. Arthroplasty using a customized total talar prosthesis designed using the computed tomography image of contralateral talus has the potential advantages of weightbearing in the earlier postoperative phase, prevention of lower extremity discrepancy, and maintenance of joint function.

Systematic investigation of intracellular trafficking behavior of one-dimensional alumina nanotubes.

Nanotube materials exhibit high drug loading capacity and controlled drug release properties, providing new opportunities for drug delivery. However, the intracellular trafficking paths of 1-dimensional (1D) nanostructured materials are poorly understood compared to their spherical counterparts, impeding the broad application of 1D materials as drug carriers. Here, we report the intracellular trafficking mechanism of nontoxic and biocompatible nanomaterials called anodic alumina nanotubes (AANTs), a model for 1D materials with a geometry that can be precisely engineered. The results indicated that AANTs enter the cells mainly by caveolin endocytosis and micropinocytosis and that cells use a novel macropinocytosis-late endosomes (LEs)-lysosomes route to transport AANTs. Moreover, liposomes (marked by DsRed-Rab18) are fully involved in the classical pathway of early endosomes (EEs)/LEs developing into lysosomes. The AANTs were delivered to the cells via two pathways: slow endocytosis recycling and GLUT4 exocytosis vesicles. The AANTs also induced intracellular autophagy and then degraded via the endolysosomal pathway. Blocking endolysosomal pathways using autophagy inhibitors prevented the degradation of AANTs through lysosomes. Our results add new insights into the pathways and mechanisms of intracellular trafficking of AANTs, and suggest that intracellular trafficking and lysosomal degradation are highly interdependent and important for efficient drug delivery, and should be evaluated together for drug carrier development.

Intranasal immunization with aluminum salt-adjuvanted dry powder vaccine.

Intranasal vaccination using dry powder vaccine formulation represents an attractive, non-invasive vaccination modality with better storage stability and added protection at the mucosal surfaces. Herein we report that it is feasible to induce specific mucosal and systemic antibody responses by intranasal immunization with a dry powder vaccine adjuvanted with an insoluble aluminum salt. The dry powder vaccine was prepared by thin-film freeze-drying of a model antigen, ovalbumin, adsorbed on aluminum (oxy)hydroxide as an adjuvant. Special emphasis was placed on the characterization of the dry powder vaccine formulation that can be realistically used in humans by a nasal dry powder delivery device. The vaccine powder was found to have "passable" to "good" flow properties, and the vaccine was uniformly distributed in the dry powder. An in vitro nasal deposition study using nasal casts of adult humans showed that around 90% of the powder was deposited in the nasal cavity. Intranasal immunization of rats with the dry powder vaccine elicited a specific serum antibody response as well as specific IgA responses in the nose and lung secretions of the rats. This study demonstrates the generation of systemic and mucosal immune responses by intranasal immunization using a dry powder vaccine adjuvanted with an aluminum salt.

Aluminium oxide nanoparticles induce structural changes in tau and cytotoxicity of the neuroblastoma cell line.

The application of nanomaterials in the healthy system may induce some neurodegenerative diseases initiated by tau folding and neuronal cell death. Herein, aluminium oxide nanoparticles (Al2O3 NPs) were synthesized and characterized by XRD, TEM, DLS and zeta potential investigations. Afterwards, the interaction of Al2O3 NPs with tau protein was investigated by fluorescence and CD spectroscopic methods. The molecular docking and molecular dynamic were also run to explore the binding site and conformational changes of tau after interaction with Al2O3 cluster. Moreover, the MTT, LDH, caspase-9/-3 and flow cytometry assays were done to explore the Al2O3 NPs-induced cytotoxicity against SH-SY5Y cells. It was revealed that Al2O3 NPs bind to tau protein and form a static complex and fold the structure of tau toward a more packed structure. Molecular docking and molecular dynamic investigations revealed that NPs bind to the hydrophilic residues of the tau segments and promote some marginal structural folding of tau segment. The cellular assays displayed that Al2O3 NPs can elicit cell mortality through membrane leakage, caspase-9/-3 activations, and induction of both apoptosis and necrosis. This data may indicate that NPs can induce some adverse effects on the biological systems.

Mid-term results of alumina ceramic unlinked total elbow arthroplasty with cement fixation for patients with rheumatoid arthritis.

Aims: The aim of this study was to report the mid-term clinical outcome of cemented unlinked J-alumina ceramic elbow (JACE) arthroplasties when used in patients with rheumatoid arthritis (RA). Patients and Methods: We retrospectively reviewed 87 elbows, in 75 patients with RA, which was replaced using a cemented JACE total elbow arthroplasty (TEA) between August 2003 and December 2012, with a follow-up of 96%. There were 72 women and three men, with a mean age of 62 years (35 to 79). The mean follow-up was nine years (2 to 14). The clinical condition of each elbow before and after surgery was assessed using the Mayo Elbow Performance Index (MEPI, 0 to 100 points). Radiographic loosening was defined as a progressive radiolucent line of >1 mm that was completely circumferential around the prosthesis. Results: The mean MEPI scores significantly improved from 40 (10 to 75) points preoperatively to 95 (30 to 100) points at final follow-up (p < 0.0001). Complications were noted in ten elbows (ten patients; 11%). Two had an intraoperative humeral fracture which was treated by fixation and united. One had a postoperative fracture of the olecranon which united with conservative treatment and one had a radial neuropathy which resolved. Further surgery was required for one with a dislocation, three with an ulnar neuropathy and one with a postoperative humeral fracture. Revision with removal of the components was performed in one elbow due to deep infection. There was no radiographic evidence of loosening around the components. With any revision surgery or revision with implant removal as the endpoint, the rates of survival up to 14 years were 93% (95% confidence interval (CI), 83.9 to 96.6) and 99% (95% CI 91.9 to 99.8), respectively, as determined by Kaplan-Meier analysis. Conclusion: With the appropriate indications, the mid-term clinical performance of the cemented JACE TEA is reliable and comparable to other established TEAs in the management of the elbow in patients with RA. Cite this article: Bone Joint J 2018;100-B:1066-73.

Nano-sized Al2O3 reduces acute toxic effects of thiacloprid on the non-biting midge Chironomus riparius.

This study focuses on interactions between nanoparticles and a pesticide. The aim was to investigate how nano-sized aluminum oxide (410 nm) can alter the toxic effects of thiacloprid, even if no sorption between particles and the insecticide takes place. Thus, our study investigated a rather unexplored interaction. We conducted our research with larvae of Chironomus riparius and used thiacloprid as test substance as its toxicity to C. riparius is well described. The used nano-Al2O3 particles where chosen due to their suitable properties. For testing the acute effects of the interaction, we exposed larvae to thiacloprid (0.5, 1.0, 2.0, and 5.0 µg/L) and nano-Al2O3 (300 and 1000 mg/L), either solely or in binary mixtures. While thiacloprid resulted in elevated mortality, nano-Al2O3 solely did not exert any effects. Moreover, we observed an aggregation of nano-Al2O3 within the lumen of the intestinal tract of the larvae. Further results showed a significantly reduced mortality of fourth instar larvae when they were exposed to mixtures of nanoparticles and the pesticide, compared to thiacloprid alone. With increasing nano-Al2O3 concentration, this effect became gradually stronger. Additionally, chemical analyses of internal thiacloprid concentrations implicate reduced uptake of thiacloprid in animals exposed to mixtures. However, as larvae exposed to thiacloprid concentrations > 0.5 µg/L showed severe convulsions, independent of the presence or concentration of nano-Al2O3, we assume that nano-Al2O3 leads to a delay of mortality and does not entirely prevent it. As sorption measurements on pristine or defecated nano-Al2O3 did not reveal any sorptive interaction with thiacloprid, we can exclude sorption-based reduction of thiacloprid bioavailability as a mechanism behind our results. Even though we used test substances which might not co-occur in the environment in the tested concentrations, our study gives evidence for an interaction besides adsorption, which is important to generally understand how nanoparticles might affect biota.

Single and combined effects of aluminum (Al2O3) and zinc (ZnO) oxide nanoparticles in a freshwater fish, Carassius auratus.

The increasing use of nanoparticles (NPs) worldwide has raised some concerns about their impact on the environment. The aim of the study was to assess the toxicity of metal oxide nanoparticles, singly or combined, in a freshwater fish (Carassius auratus). The fish were exposed for 7, 14, and 21 days to different concentrations of NPs (10 µg Al2O3.L-1, 10 µg ZnO.L-1, 10 µg Al2O3.L-1 plus 10 µg ZnO.L-1, 100 µg Al2O3.L-1, 100 µg ZnO.L-1, and 100 µg Al2O3.L-1 plus 100 µg ZnO.L-1). At the end of each exposure period, antioxidant enzyme activity (catalase, glutathione-S-transferase, and superoxide dismutase), lipid peroxidation, and histopathology were assessed in the gills and livers of C. auratus. The results show an increase in catalase (CAT) and superoxide dismutase (SOD) activity in the gills and livers of fish, especially after 14 days of exposure to single and combined NPs, followed by a reduction at 21 days. An increase in glutathione S-transferase (GST) was observed in gills after 7 days for all tested NP concentrations (single and combined); while in livers, a significant increase was determined after 14 days of exposure to 100 µg.L-1 of both single ZnO and Al2O3 NPs. Lipid peroxidation (LPO) significantly increased in gills after 7 days of exposure to 100 µg.L-1 Al2O3 NPs (single or combined). In livers, LPO increased significantly after 7 days of exposure to all tested concentrations of both single ZnO and Al2O3 (except for 10 µg Al2O3.L-1), and after 14 days of exposure to ZnO (10 and 100 µg.L-1) and Al2O3 (100 µg.L-1). The results from histological observations suggest that exposure to metal oxide NPs affected both livers and gills, presenting alterations such as gill hyperplasia and liver degeneration. However, the most pronounced effects were found in gills. In general, this study shows that the tested NPs, single or combined, are capable of causing sub-lethal effects on C. auratus, but when combined, NPs seem to be slightly more toxic than when added alone.

Phosphate substitution in an AlOOH - TLR4 adjuvant system (SPA08) modulates the immunogenicity of Serovar E MOMP from Chlamydia trachomatis.

Chlamydia trachomatis is one of the most common sexually transmitted pathogens and the development of an effective vaccine is highly desirable. The Major Outer Membrane Protein (MOMP) is one of the most abundant and immunogenic chlamydial proteins. Here we investigated the effects of phosphate substitution on the physicochemical and immunochemical properties of an experimental vaccine composed of serovar E recombinant MOMP (rMOMP) and a proprietary adjuvant system SPA08, consisting of aluminum oxyhydroxide (AlOOH) containing the TLR4 agonist E6020. An increase in phosphate substitution in the AlOOH component of the adjuvant markedly decreased the adsorptive coefficient and adsorptive capacity for both Ser E rMOMP and E6020. In vaccine formulations used for immunizations, phosphate substitution induced a decrease in the % adsorption of Ser E rMOMP without affecting the % adsorption of E6020. Immunogenicity studies in CD1 mice showed that an increase in phosphate substitution of the SPA08 adjuvant resulted in an increase in Ser E rMOMP-specific serum total IgG and IgG1 but not IgG2a titers. The degree of phosphate substitution in SPA08 also significantly increased in vitro neutralization concomitant with a decrease in proinflammatory cytokines secreted by Ser E rMOMP-restimulated splenocytes. Taken together, the results of these studies suggest that the degree of phosphate substitution in AlOOH greatly affects the adsorption of E6020 and Ser E rMOMP to AlOOH resulting in significant effects on vaccine-induced cellular and humoral responses.

Sex-Dependent Depression-Like Behavior Induced by Respiratory Administration of Aluminum Oxide Nanoparticles.

Ultrafine aluminum oxide, which are abundant in ambient and involved occupational environments, are associated with neurobehavioral alterations. However, few studies have focused on the effect of sex differences following exposure to environmental Al2O3 ultrafine particles. In the present study, male and female mice were exposed to Al2O3 nanoparticles (NPs) through a respiratory route. Only the female mice showed depression-like behavior. Although no obvious pathological changes were observed in mice brain tissues, the neurotransmitter and voltage-gated ion channel related gene expression, as well as the small molecule metabolites in the cerebral cortex, were differentially modulated between male and female mice. Both mental disorder-involved gene expression levels and metabolomics analysis results strongly suggested that glutamate pathways were implicated in sex differentiation induced by Al2O3 NPs. Results demonstrated the potential mechanism of environmental ultrafine particle-induced depression-like behavior and the importance of sex dimorphism in the toxic research of environmental chemicals.

Long-term durability of alumina ceramic heads in THA.

BACKGROUND: The optimal type of bearing for hip arthroplasty remains a matter of debate. Ceramic-on-polyethylene (CoP) bearings are frequently used in younger and more active patients to reduce wear and increase biocompatibility compared to Metal-on-Polyethylene (MoP) bearings. However, in comparison to metal heads, the fracture risk of ceramic heads is higher. In addition, ceramic head fractures pose a serious complication which often necessitates major revision surgery. To date, there are no long-term data (>20 years of follow-up) reporting fracture rates of the ceramic femoral heads in CoP bearings. The purpose of this research was to investigate long-term CoP fracture rate. METHODS: We evaluated the clinical and radiographic results of 348 cementless THAs treated with 2nd generation Biolox Al2O3 Ceramic-on-Polyethylene (CoP) bearings consecutively implanted between January 1985 and December 1989. The mean age at implantation was 57 years. The patients were followed for a minimum of 20 years. At the final 111 had died, and 5 were lost to follow-up. The cumulative incidence of ceramic head fractures in the long-term was estimated using a competing risk analysis. RESULTS: The cumulative incidence of ceramic head fracture after 22-years was estimated with a competing risk analysis at 0.29% after 22-years (SE = 2.09%; 95% - CI: 0.03-1.5%). The radiographic analysis revealed no impending failures at final follow-up. DISCUSSION/CONCLUSION: The fracture rate of second-generation ceramic heads using a CoP articulation remains very low into the third decade after cementless THA.

Proteomic analysis of flooded soybean root exposed to aluminum oxide nanoparticles.

Aluminum oxide (Al2O3) nanoparticles are used in agricultural products and cause various adverse growth effects on different plant species. To study the effects of Al2O3 nanoparticles on soybean under flooding stress, a gel-free proteomic technique was used. Morphological analysis revealed that treatment with 50 ppm Al2O3 nanoparticles under flooding stress enhanced soybean growth compared to ZnO and Ag nanoparticles. A total of 172 common proteins that significantly changed in abundance among control, flooding-stressed, and flooding-stressed soybean treated with Al2O3 nanoparticles were mainly related to energy metabolism. Under Al2O3 nanoparticles the energy metabolism was decreased compared to flooding stress. Hierarchical clustering divided identified proteins into four clusters, with proteins related to glycolysis exhibiting the greatest changes in abundance. Al2O3 nanoparticle-responsive proteins were predominantly related to protein synthesis/degradation, glycolysis, and lipid metabolism. mRNA expression analysis of Al2O3 nanoparticle-responsive proteins that displayed a 5-fold change in abundance revealed that NmrA-like negative transcriptional regulator was up-regulated, and flavodoxin-like quinone reductase was down-regulated. Moreover, cell death in root including hypocotyl was less evident in flooding-stressed with Al2O3 nanoparticles compared to flooding-treated soybean. These results suggest that Al2O3 nanoparticles might promote the growth of soybean under flooding stress by regulating energy metabolism and cell death.

Comparison of the toxicity of aluminum oxide nanorods with different aspect ratio.

Aluminum oxide nanoparticles are listed among 14 high-priority nanomaterials published by the Organization for Economic Co-operation and Development, but limited information is available on their potential hazards. In this study, we compared the toxicity of two different aluminum oxide nanorods (AlNRs) commercially available in vivo and in vitro. Considering aspect ratio, one was 6.2 ± 0.6 (long-AlNRs) and the other was 2.1 ± 0.4 (short-AlNRs). In mice, long-AlNRs induced longer and stronger inflammatory responses than short-AlNRs, and the degree reached the maximum on day 7 for both types and decreased with time. In addition, in vitro tests were performed on six cell lines derived from potential target organs for AlNPs, HEK-293 (kidney), HACAT (skin), Chang (liver), BEAS-2B (lung), T98G (brain), and H9C2 (heart), using MTT assay, ATP assay, LDH release, and xCELLigence system. Long-AlNRs generally produced stronger toxicity than short-AlNRs, and HEK-293 cells were the most sensitive for both AlNRs, followed by BEAS-2B cells, although results from 4 kinds of toxicity tests conflicted among the cell lines. Based on these results, we suggest that toxicity of AlNRs may be related to aspect ratio (and resultant surface area). Furthermore, novel in vitro toxicity testing methods are needed to resolve questionable results caused by the unique properties of nanoparticles.

In vitro toxicological assessment of iron oxide, aluminium oxide and copper nanoparticles in prokaryotic and eukaryotic cell types.

Metallic nanoparticles (NPs) have a variety of applications in different industries including pharmaceutical industry where these NPs are used mainly for image analysis and drug delivery. The increasing interest in nanotechnology is largely associated with undefined risks to the human health and to the environment. Therefore, in the present study cytotoxic and genotoxic effects of iron oxide, aluminium oxide and copper nanoparticles were evaluated using most commonly used assays i.e. Ames assay, in vitro cytotoxicity assay, micronucleus assay and comet assay. Cytotoxicity to bacterial cells was assessed in terms of colony forming units by using Escherichia coli (gram negative) and Bacillus subtilis (gram positive). Ames assay was carried out using two bacterial strains of Salmonella typhimurium TA98 and TA100. Genotoxicity of these NPs was evaluated following exposure to monkey kidney cell line, CHS-20. No cytotoxic and genotoxic effects were observed for iron oxide, and aluminium oxide NPs. Copper NPs were found mutagenic in TA98 and in TA100 and also found cytotoxic in dose dependent manner. Copper NPs induced significant (p < 0.01) increase in number of binucleated cells with micronuclei (96.6 ± 5.40) at the highest concentration (25 µg/mL). Copper NPs also induced DNA strand breaks at 10 µg/mL and oxidative DNA damage at 5 and 10 µg/mL. We consider these findings very useful in evaluating the genotoxic potential of NPs especially because of their increasing applications in human health and environment with limited knowledge of their toxicity and genotoxicity.

Effects of sub-acute exposure to TiO2, ZnO and Al2O3 nanoparticles on oxidative stress and histological changes in mouse liver and brain.

Nanomaterials are at the leading edge of the rapidly developing field of nanotechnology. However the information regarding toxicity of these nanoparticles on humans and environment is still deficient. The present study investigated the toxic effects of three metal oxide nanoparticles, TiO2, ZnO and Al2O3 on mouse erythrocytes, brain and liver. Male mice were administered a single oral dose of 500 mg/kg of each nanoparticles for 21 consecutive days. The results suggest that exposure to these nano metallic particles produced a significant oxidative stress in erythrocyte, liver and brain as evident from enhanced levels of Reactive Oxygen Species (ROS) and altered antioxidant enzymes activities. A significant increase in dopamine and norepinephrine levels in brain cerebral cortex and increased brain oxidative stress suggest neurotoxic potential of these nanoparticles. Transmission electron microscopic (TEM) analysis indicated the presence of these nanoparticles inside the cytoplasm and nucleus. These changes were also supported by the inhibition of CuZnSOD and MnSOD, considered as important biomarkers of oxidative stress. The toxic effects produced by these nanoparticles were more pronounced in the case of zinc oxide, followed by aluminum oxide and titanium dioxide, respectively. The present results further suggest the involvement of oxidative stress as one of the main mechanisms involved in nanoparticles induced toxic manifestations.

Transcutaneous delivery of micro- and nanoparticles with laser microporation.

Fractional laser ablation is one of the relatively safe and minimally invasive methods used to administer micro- and nanoparticles into the skin at sufficiently large depth. In this article, we present the results of delivery of TiO2 nanoparticles and Al2O3 microparticles into skin. Fractional laser microablation of skin was provided by a system based on a pulsed Er:YAG laser with the following parameters: the wavelength 2940 nm, the pulse energy 3.0 J, and the pulse duration 20 ms. Ex vivo and in vivo human skin was used in the study. The suspensions of titanium dioxide and alumina powder in polyethylene glycol with particle size of about 100 nm and 27 µm, respectively, were used. In the ex vivo experiments, reflectance spectra of skin samples with administered particles were measured and histological sections of the samples were made. In the in vivo experiment, reflectance spectroscopy, optical coherence tomography, and clinical photography were used to monitor the skin status during one month after suspension administering. It is shown that particles can be delivered into dermis up to the depth 230 µm and distributed uniformly in the tissue. Spectral measurements confirm that the particles stay in the dermis longer than 1 month.

Murine pulmonary responses after sub-chronic exposure to aluminum oxide-based nanowhiskers.

BACKGROUND: Aluminum oxide-based nanowhiskers (AO nanowhiskers) have been used in manufacturing processes as catalyst supports, flame retardants, adsorbents, or in ceramic, metal and plastic composite materials. They are classified as high aspect ratio nanomaterials. Our aim was to assess in vivo toxicity of inhaled AO nanowhisker aerosols. METHODS: Primary dimensions of AO nanowhiskers specified by manufacturer were 2-4 nm x 2800 nm. The aluminum content found in this nanomaterial was 30% [mixed phase material containing Al(OH)3 and AlOOH]. Male mice (C57Bl/6 J) were exposed to AO nanowhiskers for 4 hrs/day, 5 days/wk for 2 or 4 wks in a dynamic whole body exposure chamber. The whiskers were aerosolized with an acoustical dry aerosol generator that included a grounded metal elutriator and a venturi aspirator to enhance deagglomeration. Average concentration of aerosol in the chamber was 3.3 ± 0.6 mg/m3 and the mobility diameter was 150 ± 1.6 nm. Both groups of mice (2 or 4 wks exposure) were necropsied immediately after the last exposure. Aluminum content in the lung, heart, liver, and spleen was determined. Pulmonary toxicity assessment was performed by evaluation of bronchoalveolar lavage (BAL) fluid (enumeration of total and differential cells, total protein, activity of lactate dehydrogenase [LDH] and cytokines), blood (total and differential cell counts), lung histopathology and pulmonary mechanics. RESULTS: Following exposure, mean Al content of lungs was 0.25, 8.10 and 15.37 µg/g lung (dry wt) respectively for sham, 2 wk and 4 wk exposure groups. The number of total cells and macrophages in BAL fluid was 2-times higher in animals exposed for 2 wks and 6-times higher in mice exposed for 4 wks, compared to shams (p < 0.01, p < 0.001, respectively). However no neutrophilic inflammation in BAL fluid was found and neutrophils were below 1% in all groups. No significant differences were found in total protein, activity of LDH, or cytokines levels (IL-6, IFN-γ, MIP-1α, TNF-α, and MIP-2) between shams and exposed mice. CONCLUSIONS: Sub-chronic inhalation exposures to aluminum-oxide based nanowhiskers induced increased lung macrophages, but no inflammatory or toxic responses were observed.

The profile of ß-amyloid precursor protein expression of rats induced by aluminum.

The environmental agent aluminum has been extensively investigated for a potential relationship with amyloid precursor protein (APP) expression. Despite many investigations, there is at present no definite proof from which to draw a conclusion. Since APP is an integral membrane protein expressed in different tissues and capable of fluxes across the blood-brain barrier (BBB), which may ultimately affect APP level in brain, it is necessary to assess the expression profile among vital body organs. The present study compared aluminum oxide and aluminum chloride injected rats with control rats (saline treated) to observe if aluminum affected APP expression patterns in different organs by immunohistochemistry (IHC). The expression of APP was observed in the brain of aluminum chloride treated rats and in the liver of aluminum oxide injected group. Results of double IHC staining showed that it is Kupffer cells, which are located in liver sinus and expressed APP after aluminum oxide treatment. Oxidative stress is suggested as the potential pathway that aluminum chloride exert effects in brain. These results suggest that different aluminum compounds may impact the expression of APP in brain and liver tissues. The mechanism that aluminum induced liver APP expression still needs further investigation.