Toll-like receptor 4 is a key regulator of asthma exacerbation caused by aluminum oxide nanoparticles via regulation of NF-κB phosphorylation.

Aluminum oxide nanoparticles (Al2O3 NPs) have recently been reported to cause an inflammatory response in the lungs, and studies are being conducted on their adverse effects, especially in patients with underlying lung diseases such as asthma. However, the underlying mechanism of asthma aggravation caused by Al2O3 NPs remains unclear. This study investigated whether Al2O3 NPs exacerbate ovalbumin (OVA)-induced asthma and focused on the correlation between toll-like receptor 4 (TLR4) signaling and Al2O3 NP-induced asthma exacerbation. Al2O3 NP exposure in asthmatic mice resulted in increased inflammatory cell counts in the lungs, airway hyperresponsiveness, and increased levels of inflammatory cytokines compared with only OVA-induced mice, and excessive secretion of mucus was observed in the airways. Moreover, Al2O3 NP exposure in OVA-induced mice increased the expression levels of TLR4, phospho-nuclear transcription factor-kappa B (p-NFκB), myeloid differentiation factor 88 (MyD88), and phospho-NF kappa B inhibitor alpha (p-IκBα). Furthermore, in the lungs of TLR4 knockout mice exposed to Al2O3 NPs and in a human airway epithelial cell line with down regulated TLR4, the expression levels of MyD88, p-NFκB, and p-IκBα were decreased, and asthma-related allergic responses were reduced. Therefore, we demonstrated that TLR4 is important for aggravation of asthma induced by Al2O3 NPs, and this study provides useful information regarding as yet undiscovered novel target signaling.

Edible algae (Ecklonia cava) bioprocessed with mycelia of shiitake (Lentinula edodes) mushrooms in liquid culture and its isolated fractions protect mice against allergic asthma.

BACKGROUND: Ecklonia cava is an edible marine brown alga harvested from the ocean that is widely consumed in Asian countries as a health-promoting medicinal food The objective of the present study is to evaluate the anti-asthma mechanism of a new functional food produced by bioprocessing edible algae Ecklonia cava and shiitake Lentinula edodes mushroom mycelia and isolated fractions. METHODS: We used as series of methods, including high performance liquid chromatography, gas chromatography, cell assays, and an in vivo mouse assay to evaluate the asthma-inhibitory effect of Ecklonia cava bioprocessed (fermented) with Lentinula edodes shiitake mushroom mycelium and its isolated fractions in mast cells and in orally fed mice. RESULTS: The treatments inhibited the degranulation of RBL-2H3 cells and immunoglobulin E (IgE) production, suggesting anti-asthma effects in vitro. The in vitro anti-asthma effects in cells were confirmed in mice following the induction of asthma by alumina and chicken egg ovalbumin (OVA). Oral administration of the bioprocessed Ecklonia cava and purified fractions suppressed the induction of asthma and was accompanied by the inhibition of inflammation- and immune-related substances, including eotaxin; thymic stromal lymphopoietin (TSLP); OVA-specific IgE; leukotriene C4 (LTC4); prostaglandin D2 (PGD2); and vascular cell adhesion molecule-1 (VCAM-1) in bronchoalveolar lavage fluid (BALF) and other fluids and organs. Th2 cytokines were reduced and Th1 cytokines were restored in serum, suggesting the asthma-induced inhibitory effect is regulated by the balance of the Th1/Th2 immune response. Serum levels of IL-10, a regulatory T cell (Treg) cytokine, were increased, further favoring reduced inflammation. Histology of lung tissues revealed that the treatment also reversed the thickening of the airway wall and the contraction and infiltration of bronchial and blood vessels and perialveolar inflammatory cells. The bioprocessed Ecklonia cava/mushroom mycelia new functional food showed the highest inhibition as compared with commercial algae and the fractions isolated from the bioprocessed product. CONCLUSIONS: The in vitro cell and in vivo mouse assays demonstrate the potential value of the new bioprocessed formulation as an anti-inflammatory and anti-allergic combination of natural compounds against allergic asthma and might also ameliorate allergic manifestations of foods, drugs, and viral infections.

Alumina Ceramic Exacerbates the Inflammatory Disease by Activation of Macrophages and T Cells.

(1) Background: Aluminum oxide (Al2O3) ceramic is one of the materials used for artificial joints, and it has been known that their fine particles (FPs) are provided by the wear of the ceramic. Al2O3 FPs have been shown to induce macrophage activation in vitro; however, the inflammatory effect in vivo has not been studied. (2) Methods: We examined the in vivo effect of Al2O3 FPs on the innate and adaptive immune cells in the mice. (3) Results: Al2O3 FPs promoted the activation of spleen macrophages; however, conventional dendritic cells (cDCs), plasmacytoid DCs (pDCs), and natural killer (NK) cells were not activated. In addition, increases in the CD4 and CD8 T cells was induced in the spleens of the mice treated with Al2O3 FPs, which differentiated into interferon-gamma (IFN-γ)-producing helper T1 (Th1) and cytotoxic T1 (Tc1) cells. Finally, the injection of Al2O3 FPs exacerbated dextran sulfate sodium (DSS)-induced inflammation in the colon, mediated by activated and increased number of CD4 and CD8 T cells. (4) Conclusions: These data demonstrate that FPs of Al2O3 ceramic may contribute to the exacerbation of inflammatory diseases in the patients.

Effects of Bauxite and Alumina Exposure on Incidence of Cancer - Meta-analysis.

Bauxite is an ore from which Aluminium is produced. Malaysia, once the leading producer of bauxite has reduced production as mining activity has caused community outrage. Due to concerns about health concerns, rising pollution and environmental hazards, the government has revoked the licenses of bauxite miners. We therefore did a meta-analysis to assess the relationship between exposure to Bauxite and Alumina with incidence of various types of cancers. Bauxite mines and alumina refineries. Individuals of all ages exposed to Bauxite and Alumina. Exposure to bauxite and alumina. Incidence due to overall cancers and specific types of cancers. Exposure to bauxite and alumina did not cause variations in incidence of overall cancer and specific types of cancer such as cancer of lip, cancer of the oral cavity and pharynx, cancer of digestive organs and others. We conclude that there is no evidence that bauxite or alumina exposure cause increase incidence of cancer but due to the small number of studies included in this review, we recommend more cohort studies to be done in future.

Biocompatibility of alumina-based biomaterials-A review.

In today's medicine world, alumina-based biomaterials owing to their excellent biomechanical, and biocompatibility properties play a key role in biomedical engineering. However, the literature still suffers from not having a valid database regarding the protein adsorption and subsequently cell responses to these surfaces. Proteins by adsorption on biomaterials surfaces start interpreting the construction and also arranging the biomaterials surfaces into a biological language. Hence, the main concentration of this review is on the protein adsorption and subsequently cell responses to alumina's surface, which has a wide range biomedical applications, especially in dentistry and orthopedic applications. In the presented review article, the general principles of foreign body response mechanisms, and also the role of adsorbed proteins as key players in starting interactions between cells and alumina-based biomaterials will be discussed in detail. In addition, the essential physicochemical, and mechanical properties of alumina surfaces which significantly impact on proteins and cells responses as well as the recent studies that have focused on the biocompatibility of alumina will be given. An in depth understanding of how the immune system interacts with the surface of alumina could prove the pivotal importance of the biocompatibility of alumina on its success in tissue engineering after implantation in body.

Artificial shear stress effects on leukocytes at a biomaterial interface.

Medical devices, such as ventricular assist devices (VADs), introduce both foreign materials and artificial shear stress to the circulatory system. The effects these have on leukocytes and the immune response are not well understood. Understanding how these two elements combine to affect leukocytes may reveal why some patients are susceptible to recurrent device-related infections and provide insight into the development of pump thrombosis. Biomaterials-DLC: diamond-like carbon-coated stainless steel; Sap: single-crystal sapphire; and Ti: titanium alloy (Ti6 Al4 V) were attached to the parallel plates of a rheometer. Whole human blood was left between the two discs for 5 minutes at +37°C with or without the application of shear stress (0 s-1 or 1000 s-1 ). Blood was removed and used for complete blood cell counts, flow cytometry (leukocyte activation, cell death, microparticle generation, phagocytic ability, and reactive oxygen species [ROS] production), and the production of pro-inflammatory cytokines. L-selectin expression on monocytes was decreased when blood was exposed to the biomaterials both with and without shear. Applying shear stress to blood on a Sap and Ti surface led to activation of neutrophils shown as decreased L-selectin expression. Sap and Ti blunted the LPS-stimulated macrophage migration inhibitory factor (MIF) production, most notably when sheared on Ti. The biomaterials used here have been shown to activate leukocytes in a static environment. The introduction of shear appears to exacerbate this activation. Interestingly, a widely accepted biocompatible material (Ti) utilized in many different types of devices has the capacity for immune cell activation and inhibition of MIF secretion when combined with shear stress. These findings contribute to our understanding of the contribution of biomaterials and shear stress to recurrent infections and vulnerability to sepsis in some VAD patients as well as pump thrombosis.

[Using of specialized food for the workers with skin occupational eczema of perlite production].

The research was conducted with participation of the perlite production workers with professional eczema (165 people in the main group and 152 from the control group without skin pathology). The effectiveness of the use of a specialized prophylactic food in the diet of workers was assessed on the basis of the study of the dynamics of the indicators of nutritional and clinical status. Inclusion of kissel, containing pectin, vitamin A (300% from RDA), vitamin E and zinc (40% from RDA), biologically active substances of plant origin in the diet of the examined against the background of the course of complex therapy, has resulted in a positive influence on individual laboratory values, demonstrating the optimization of metabolic processes, which characterize the pathogenesis of skin inflammation. Thus, the concentration of ascorbic acid in blood serum statistically significant (p<0.05) increased by 30.0%, tocopherol - by 36.3%, carotenoids - by 27.3%, phosphorus - by 28.9%, calcium level elevated by 16.3% (p<0.10). There was a decrease in the level of MDA in blood serum by 12.3% (p<0.05) and an increase in catalase activity by 12.2% (p>0.05). There was a tendency to reduce itching, infiltration, erythematous and eczematous manifestations of the disease. The data obtained make it possible to consider the use of a specialized food product of dietary preventive nutrition by workers in pearlite production as a mean to enhance the body's adaptive reserves and to prevent the occurrence, progression and development of occupational skin diseases (eczema) in the workplace.

Adapter Sleeves Are Not Needed to Reduce the Risk of Fracture of a New Ceramic Head Implanted on a Well-Fixed Stem.

The purpose of this study was to assess (1) the prevalence of the fracture of ceramic heads implanted on used trunnions of well-fixed stems without using a titanium adapter sleeve; (2) the prevalence of trunnionosis secondary to fretting and/or corrosion at the trunnion of the well-fixed stem; and (3) clinical and radiographic results and the survival rate of the revised acetabular components. Eighty-eight patients (100 hips) underwent isolated revision of the acetabular components for polyethylene wear and osteolysis of the acetabulum. The study group consisted of 70 men and 18 women with a mean age of 52.8 years (range, 31-54 years) when the primary total hip arthroplasty was performed. Evidence of fretting and corrosion of the trunnion of all prostheses was examined macroscopically using a magnifying lens. Degree of fretting and corrosion of the trunnion was assessed using a 4-point scoring technique. A new 36-mm alumina delta ceramic head was implanted on the trunnion of a well-fixed stem without using a titanium adapter sleeve in all hips. The mean follow-up after revision of the acetabular component was 12.8 years (range, 10-14 years). Among the 100 new ceramic heads implanted on a well-fixed stem, no fracture of the ceramic head occurred at a mean follow-up of 12.8 years. The median fretting and corrosion scores for the trunnions were 1.5±1.1 and 1.3±0.9 points, respectively. The mean Harris hip score at the final follow-up was 89±15 points (range, 63-100 points). Survivorship of the revised acetabular components at 14 years was 95% (95% confidence interval, 87.6%-98.6%). [Orthopedics. 2018; 41(3):158-163.].

Alumina Biocompatibility.

Alumina (Al2O3) ceramic is widely used for medical devices and its biocompatibility is well known and is reported in articles and textbooks. However, finding proof of this assertion gathered over more than 40 years can be challenging. We performed a literature review about alumina biocompatibility to compile data from the literature. We searched for articles on the biocompatibility of alumina in relation to the ISO 10993-1 International Standard, which defines the biocompatibility of biomaterials. For every biological effect listed in the norm, such as cytotoxicity, sensitization, implantation, and genotoxicity, in vitro and in vivo tests in animals and humans did not reveal any abnormal biological response. Proof for the the well-known biocompatibility of alumina is summarized in this review.

Removal of unwanted hair: efficacy, tolerability, and safety of long-pulsed 755-nm alexandrite laser equipped with a sapphire handpiece.

Due to the difference in refraction coefficients between air and the corneal epithelium, irradiation of the skin with a light source can lead to reflection of the energy and its leakage to the skin causes epidermal injury. All of which decreases the efficacy of treatment. We evaluated cooling sapphire handpieces' efficacy in decreasing pain and epidermal injuries and enhancing the treatment outcome in laser hair removal. A total of 49 patients with Fitzpatrick skin types of II to IV were treated for laser hair removal on face, limbs, inguinal, and axillary areas with pulsed 755-nm alexandrite laser equipped with a sapphire handpiece and the cooling system. Hair counts were performed by two independent observers at the baseline and 3 months after the final treatment. A marked reduction in hair regrowth was noted 3 months after the final treatment in all body locations studied. Clinical hair reduction was observed and fully assessed. There were no serious side effects with an average pain score of 4.6 out of 40. The cooled sapphire cylinder tip has been shown to minimize epidermal injury and reduce the system energy leaks to the skin.

Size-Dependent Neurotoxicity of Aluminum Oxide Particles: a Comparison Between Nano- and Micrometer Size on the Basis of Mitochondrial Oxidative Damage.

Aluminum nanoparticles (AlNPs) are among the most abundantly produced nanosized particles in the market. There is limited information about the potential harmful effects of aluminum oxide due to its particle size on human health. Considering the toxic effects of Al on brain as its target tissue, in this study, the toxicity of nanoparticles, microparticles, and ionic forms of Al on rat brain and isolated mitochondria was evaluated. Sixty male Wistar rats were divided into ten groups (six rats each), in which group I was the control, and the other groups were administered different doses of Al nanoparticles, Al microparticles (AlMP), and Al ionic forms (2, 4, and 8 mg/kg, i.p.) for 28 days. After 24 h, the animals were killed, brain tissue was separated, the mitochondrial fraction was isolated, and oxidative stress markers were measured. Also, mitochondrial function was assayed by MTT test. The results showed that all forms of Al particles induced ROS formation, lipid peroxidation, protein oxidation, glutathione depletion, mitochondrial dysfunction, and gait abnormalities in a dose-dependent manner. In addition, Al particles decreased mitochondrial membrane potential. These data indicated that oxidative stress might contribute to the toxicity effects of Al. Comparison of oxidative stress markers between all forms of Al revealed that the toxic effect of AlNP on brain tissue was substantially more than that caused by AlMP and bulk form. This study showed more neurotoxicity of AlNPs compared to other forms on brain oxidative damage that probably is due to more penetration into the brain.

Self-defense of Escherichia coli against damages caused by nanoalumina.

Although studies showed effects of nanoalumina (nano-Al2O3) on Escherichia coli, no study completely provides understanding on how bacterial cells respond to damages, especially on how they initiate self-defense. In this study, we showed three types of responses of E. coli to damages caused by nano-Al2O3. Live, dead, and injured, bacteria showed improved survival rates reaching 104%, 116%, and 104% after exposure to 0.1, 1, and 10mmol/L of nano-Al2O3 respectively. Survival rates improved from 100% to 114%, corresponding to an exposure time of 0-9h, and from 100% to 127%, corresponding to 0-1000µg/L Al3+. Improvements were noted in survival rates of E. coli K12 MG1655, HB101, DH5α, and K12 MG1655 △lexA treated by nano-Al2O3 in Luria-Bertani (LB) exposure system or K12 MG1655 in LB, normal saline(NS) and H2O exposure system. Bacterial cells transformed from long rods to ellipsoidal or nearly spherical as form of self-preservation mechanism; this phenomenon may be related to changes in membrane potential induced by free Al3+ released from nano-Al2O3 particles. Molecular mechanism of this response involved inhibited gene expression of sythesis and metabolism of carbohydrates, lipids and proteins. Findings presented in this study may improve understanding of potential danger of nanomaterials and control their spread to environmen.

Studying the General Toxicity and Cumulative Properties of a Radiopharmaceutical Nanocolloid, (99m)Tc-Al2O3.

We studied toxicity of a new Russian radiopharmaceutical Nanocolloid, (99m)Tc-Al2O3. Tests for acute toxicity showed that this agent belongs to a class of moderate-toxicity substances and does not have cumulative properties. The evaluation of subchronic toxicity after subcutaneous injection of this product to rats (0.04, 0.2, and 0.4 ml/kg) and rabbits (0.02 and 0.2 ml/kg) for 7 days did not reveal changes in the general state, temperature, body weight, indices of the peripheral blood and bone marrow, functions of the heart, liver, kidneys, and nervous system, and morphological characteristics of the internal organs in animals. The drug does not produce a local irritant effect.

Results of revision of total hip arthroplasty for alumina ceramic-on-ceramic bearing fracture.

PURPOSE: The purpose of this study was to compare the results of revision total hip arthroplasty after fracture of primary ceramic components using different type of revision bearing surfaces. METHODS: We analysed the results of 16 patients with a follow-up more than 3 years after first revision. 6 were revised to ceramic-on-ceramic (CoC) bearing, 9 to metal-on-polyethylene (MoP) and 1 to ceramic-on-cross-linked polyethylene (CoXLP) bearing. RESULTS: The mean follow-up was 87 months. Patients with revision to CoC had higher Harris Hip Score (HHS) of 89 points in comparison to the patients with revision to MoP with 84 points. Radiographic examinations revealed visible eccentric polyethylene wear with osteolysis in 3 out of 9 patients revised to MoP. There were no detrimental x-ray changes in patients revised to CoC components. CONCLUSIONS: We consider CoC as the best option at revision operation for ceramic component fracture.

Inflammation in induced sputum after aluminium oxide exposure: an experimental chamber study.

INTRODUCTION: Workers in aluminium production are exposed to a complex mixture of particles and gases potentially harmful to the airways, among them aluminium oxide (Al2O3). With the use of an exposure chamber, we aimed to examine the effects of short-term controlled exposure to Al2O3 on lung function and inflammatory markers in healthy volunteers. METHODS: 15 men (age 19-31) were exposed in random order to clean air or Al2O3 particles (3.8-4.0 mg/m(3)) for 2 h including 30 min exercise (stationary bike, 75 W). The permissible exposure level (PEL) for Al2O3 by Occupational Safety and Health Administration, USA, is 5 mg/m(3) time weighted average (TWA). Sham and particle exposures were separated by at least 2 weeks. Spirometry was carried out, and induced sputum and blood samples were collected 48 h before and 4 and 24 h after exposure. RESULTS: Levels of sputum neutrophils (mean (±SEM)) was increased 24 h post-Al2O3 vs pre-Al2O3 exposure (43% (4) vs 31% (4), p=0.01) and the protein level of interleukin (IL)-8 had a 4.8 (0.9)-fold change increase 24 h after exposure (p<0.01). Following Al2O3 exposure, gene signatures in sputum were significantly increased related to several pathways. CONCLUSIONS: The present study suggests that controlled exposure to Al2O3 particles at levels below PEL (TWA) induces airway inflammation in healthy humans marked by elevated neutrophils and elevated IL-8. In addition, increased expression of genes associated with several biological processes was observed in sputum. Interestingly, inhaled Al2O3-induced effects were localised to the airways and not systemic.

Investigation of the cytotoxicity of aluminum oxide nanoparticles and nanowires and their localization in L929 fibroblasts and RAW264 macrophages.

The biological responses of aluminum oxide (Al2 O3 ) nanoparticles (NPs) and nanowires (NWs) in cultured fibroblasts (L929) and macrophages (RAW264) were evaluated from their cytotoxicities and micromorphologic properties. Cultured cells were exposed to Al2 O3 NPs (13 nm diameter) and Al2 O3 NWs (2-6 × 200-400 nm). Cytotoxicity and genotoxicity were examined by immunostaining with fluorescence microscopy, and nanomaterial localization was studied by using scanning electron microscopy and transmission electron microscopy. The NPs were cytotoxic and genotoxic, whereas the NWs were not. The scanning electron microscopy images showed that the NPs aggregate more on the cell surface than do the NWs. The transmission electron microscopy images showed that the NPs were internalized into the vesicle and nuclei, for both cell types. In contrast, numerous solid NWs were observed as large aggregates in vesicles, but not in nuclei. Nuclear damage was confirmed by measuring cell viability and by immunostaining for NPs. The chemical changes induced by the NPs in the vesicles or cells may cause cell damage because of their large surface area per volume. The extent of NW entrapment was not sufficient to lower the viability of either cell type.

Hard and soft tissue responses to three different implant materials in a dog model.

The aim of this study was to assess hard and soft tissue responses using three dental implants made of different materials. Implants made of titanium (Ti), yttria-stabilized tetragonal zirconia polycrystals (Y-TZP) and ceria partially stabilized zirconia/alumina nanocomposite (Ce-TZP/Al2O3) were used in a dog model. Five male beagles were sacrificed at three months after implantation, and harvested mandible were observed and analyzed. Histological observations were similar in all groups. There were no significant differences in any histomorphometric parameters. Our results suggested the possibility of Ce-TZP/Al2O3 as a dental implant material, similar to Ti and Y-TZP.

[STUDYING ACUTE TOXICITY OF NEW RADIOPHARMACEUTICAL 99MTC-AL2O3 NANOCOLLOIDS FOR ONCOLOGICAL DIAGNOSTICS].

The acute toxicity of a new drug based on nanocolloidal gamma alumina labeled with technetium-99m (99mTc) has been studied on 80 rats (40 females and 40 males) and 80 mice (40 females and 40 males) with intraperitoneal and subcutaneous drug administration. A single administration of the pharmacological agent was followed by observation of the survival of animals for 14 days with determining tolerable, toxic, and lethal doses for intraperitoneal and subcutaneous administration according to the Litchfield - Wilcoxon method, establishing the causes of animal death within 14 days of observation, and studying the drug influence on the general condition and some functional and morphological indices. Based on the established boundaries of toxicity and the classification of toxicity, the 99mTc-Al2O3 nanocolloids can be classified into conditionally moderately toxic substances. The actual values of LD5 of the radiopharmaceutical fall in the range of large doses. The safety factor for the drug studied significantly exceeds the minimum permissible value of 100.