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.

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.

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.

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.

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.

Nanostructured alumina-coated implant surface: effect on osteoblast-related gene expression and bone-to-implant contact in vivo.

PURPOSE: The use of nanotechnology to enhance endosseous implant surfaces may improve the clinical control of interfacial osteoblast biology. This study investigated the influence of a nanostructure-coated implant surface on osteoblast differentiation and its effects on bone-to-implant contact (BIC) and removal torque values. MATERIALS AND METHODS: Titanium disks were machined (M) or machined and subsequently treated by acid etching (Ac) or by dipping in an aluminum oxide solution (Al2O3). Surfaces were characterized by scanning electron microscopy, atomic force microscopy, and x-ray microanalysis. For the in vitro experiment, rat mesenchymal stem cells (rMSCs) were grown in osteogenic supplements on the disk surfaces for 3 days. Real-time polymerase chain reaction (PCR) was used to measure mRNA levels of several gene products (bone sialoprotein, osteocalcin, osteopontin, and RUNX-2). For the in vivo experiment, titanium implants were placed in rat tibiae and harvested after 3 to 21 days for measurement of bone-specific mRNA levels by real-time PCR. Removal torque and BIC were measured 3 to 56 days after placement. RESULTS: Average height deviation (Sa, in nm) values for M, Ac, and Al2O3 implants were 86.5, 388.4, and 61.2, respectively. Nanostructured Al2O3 topographic features applied to machined implants promoted MSC commitment to the osteoblast phenotype. Greater bone-specific gene expression was observed in tissues adjacent to Al2O3 implants, and associated increases in BIC and torque removal were noted. CONCLUSION: Nanostructured alumina may directly influence cell behavior to enhance osseointegration.

Effect of aluminum oxide-blasted implant surface on the bone healing around implants in rats submitted to continuous administration of selective cyclooxygenase-2 inhibitors.

PURPOSE: The continual use of selective cyclooxygenase-2 (COX-2) inhibitors may have a negative impact on bone repair around titanium implants. Because modified implant surfaces could be considered an important strategy to increase success rates in some conditions that interfere in bone healing, the aim of this study was to investigate whether an aluminum oxide (Al2O3)-blasted implant surface could reduce the negative action promoted by the continuous administration of selective COX-2 inhibitors on bone healing around implants. MATERIALS AND METHODS: Thirty Wistar rats received one titanium implant (machined or Al2O3-blasted surface) in each tibia and were randomly assigned to one of the following groups: saline (n = 14) or meloxicam (n = 16); each was administered daily for 60 days. Bone-to-implant contact (BIC), bone area (BA) within the limits of threads, and bone density (BD) in a zone lateral to the implant were examined in undecalcified sections. RESULTS: The Al2O3-blasted surface resulted in significantly increased BIC in both groups, and meloxicam significantly reduced bone healing around implants (P < .05). For the machined surface, significant differences were observed for BIC (39.48 +/- 10.18; 25.23 +/- 9.29), BA (60.62 +/- 4.09; 42.94 +/- 8.12), and BD (56.31 +/- 3.64; 49.30 +/- 3.15) in the saline and meloxicam groups, respectively. For the Al2O3-blasted surface, data analysis also demonstrated significant differences for BIC (45.92 +/- 11.34; 33.30 +/- 7.56), BA (61.04 +/- 4.39; 44.89 +/- 7.11), and BD (58.77 +/- 2.93; 50.04 +/- 3.94) for the saline and meloxicam groups, respectively. CONCLUSIONS: The Al2O3-blasted surface may increase BIC; however, it does not reverse the negative effects promoted by a selective COX-2 inhibitor on bone healing around implants.

Glia activation induced by peripheral administration of aluminum oxide nanoparticles in rat brains.

With the wide application of nanoscaled particles, the risk of human exposure to these particles has been markedly increased. However, knowledge about their safety falls far behind the utility of these nanoparticles. Here we have analyzed the activation of brain microglia and astrocytes, which are sensitive to changes of brain environment after peripheral exposure to nanoscaled aluminum oxide suspension. Sprague-Dawley rats (six rats per treatment) were intraperitoneally injected once every second day for 30 or 60 days with nanoscaled aluminum oxide (NSAO; 1 mg/kg or 50 mg/kg), non-nanoscaled aluminum oxide (nNSAO, 1 mg/kg), or vehicle (saline). After 60 days' exposure the numbers of ED1+, GFAP+, and nestin+ cells in cortex and hippocampus were significantly higher in NSAO-treated rats than nNSAO- or vehicle-treated rats; thus, compared with nNSAO, NSAO has potential effects on the innate immune system of rat brain. This should be considered when evaluating the toxicological effects of nanosized particles. FROM THE CLINICAL EDITOR: Sprague-Dawley rats were intraperitoneally injected with nanosized aluminum oxide, (NSAO); non-nanoscaled aluminum oxide, or vehicle (saline). The numbers of ED1+, GFAP+, and nestin+ cells in cortex and hippocampus were significantly higher in NSAO-treated rats than nNSAO- or vehicle-treated rats; thus, NSAO has potential effects on the innate immune system of rat brain.

Retrospective analysis of 4-week inhalation studies in rats with focus on fate and pulmonary toxicity of two nanosized aluminum oxyhydroxides (boehmite) and pigment-grade iron oxide (magnetite): the key metric of dose is particle mass and not particle surface area.

This paper compares the pulmonary toxicokinetics and toxicodynamics of three different types of poorly soluble dusts examined in repeated rat inhalation bioassays (6h/day, 5 days/week, 4 weeks). In these studies the fate of particles was studied during a 3-6-month postexposure period. This retrospective analysis included two types of aluminum oxyhydroxides (AlOOH, boehmite), high purity calcined, and agglomerated nanosized aluminas of very low solubility with primary isometric particles of 10 or 40nm, and synthetic iron oxide black (Fe(3)O(4) pigment grade). Three metrics of dose (actual mass concentration, surface area concentration, mass-based lung burden) were compared with pulmonary toxicity characterized by bronchoalveolar lavage. The results of this analysis provide strong evidence that pulmonary toxicity (inflammation) corresponds best with the mass-based cumulative lung exposure dose. The inhalation study with a MMAD of approximately 0.5microm yielded a higher pulmonary dose than MMADs in the range of 1-2microm, a range most commonly used in repeated exposure inhalation studies. Hence, a key premise for the dosimetric adjustment across species is that comparable lung tissue doses should cause comparable effects. From that perspective, the determination of mass-based pulmonary lung burdens appears to be amongst the most important and critical nominator of dose and dose-related pulmonary toxicity.

Influence of protein conformation and adjuvant aggregation on the effectiveness of aluminum hydroxide adjuvant in a model alkaline phosphatase vaccine.

The mechanism(s) of the enhancement of the immune response by addition of aluminum salt adjuvants to parenterally administered protein-based vaccines is still the subject of debate. It has been hypothesized, however, that destabilization of the antigen structure on the surface of the adjuvant may be important for eliciting immune response. Also, it has been suggested that immune response to adjuvanted vaccines is reduced if the adjuvant particles become aggregated before administration because of processing steps such as freeze-drying. In this study, we tested these hypotheses and examined the immune response in a murine model to various liquid, freeze-dried, and spray freeze-dried formulations of a model vaccine, bovine intestinal alkaline phosphatase adsorbed on aluminum hydroxide. Enzymatic activity of the alkaline phosphatase was used as a sensitive indicator of intact native antigen structure. By manipulating the secondary drying temperature during lyophilization, vaccines were produced with varying levels of alkaline phosphatase enzymatic activity and varying degrees of adjuvant aggregation, as assessed by particle size distribution. Anti-alkaline phosphatase titers observed in immunized mice were independent of both the antigen's retained enzymatic activity and the vaccine formulation's mean particle diameter.

Evaluation of histologic and electron microscopic changes after novel treatment using combined microdermabrasion and ultrasound-induced phonophoresis of human skin.

BACKGROUND: Mechanical exfoliation using microdermabrasion has been used as a minimally invasive treatment of photodamage, as well as to improve absorption of topical agents. Phonophoresis, a method of electrically assisted percutaneous delivery of macromolecules, relies on ultrasonic waves producing alterations within the stratum corneum that result in increased absorption. OBJECTIVE: To determine the effects on photodamaged facial skin that resulted from the ultrasound-enhanced delivery of a combined hyaluronic acid, retinol, and peptide-containing complex following microdermabrasion. METHODS: Seven individuals, aged 40-65, with Fitzpatrick skin types I-III and class I-III rhytids, underwent eight weekly aluminum oxide crystal microdermabrasion procedures (Parisian Peel; Aesthetic Technologies, Golden, CO, USA), followed by administration of a topical combined hyaluronic acid, retinol, and peptide-containing complex, propelled through ultrasound phonophoresis. The participants continued manual twice-daily application of the topical complex between treatments. Clinical evaluation included digital photography, and patient and investigator assessment of changes in skin dryness, texture, brightness, tone, and rhytids. The 3-month post-treatment histologic evaluation consisted of pre- and post-treatment biopsies evaluated for microscopic and ultrastructural changes. RESULTS: An overall mild clinical improvement in the skin was noted. A slight increase in vascularity within the papillary dermis, increased reticulin stain (type III collagen), and ultrastuctural evidence of increased type I collagen indicate dermal injury with resulting new collagen formation. CONCLUSION: Microdermabrasion followed by ultrasonic phonophoretic application of topical products represents a novel dermal delivery approach to photorejuvenation.

Use of lanthanide-grafted inorganic nanoparticles as effective contrast agents for cellular uptake imaging.

The improvement of commonly used Gd3+ -based MRI agents requires the design of new systems with optimized in vivo efficacy, pharmacokinetic properties, and specificity. To design these contrast agents, two parameters are usually considered: increasing the number of coordinated water molecules or increasing the rotational correlation time by increasing molecular weight and size. This has been achieved by noncovalent or covalent binding of low-molecular weight Gd3+ chelates to macromolecules or polymers. The grafting of these high-spin paramagnetic gadolinium chelates on metal oxide nanoparticles (SiO2, Al2O3) is proposed. This new synthetic strategy presents at least two main advantages: (1) a high T1-relaxivity for MRI with a 275% increase of the MRI signal and (2) the ability of nanoparticles to be internalized in cells. Results indicate that these new contrast agents lead to a huge reconcentration of Gd3+ paramagnetic species inside microglial cells. This reconcentration phenomenon gives rise to high signal-to-noise ratios on MR images of cells after particle internalization, from 1.4 to 3.75, using Al2O3 or SiO2 particles, respectively. The properties of these new particles will be further used to get new insight into gene therapy against glioma, using microglial cells as vehicles to simultaneously transport a suicide gene and contrast agents. Since microglia are chemoattracted to brain tumors, the presence of these new contrast agents inside the cells will lead to a better MRI determination of the in vivo location, shape, and borders of the tumors. These Gd3+-loaded microglia can therefore provide effective localization of tumors by MRI before applying any therapeutic treatment. The rate of carcinoma remission following a suicide gene strategy is also possible.