ß-sitosterol Protects against Aluminium Chloride-mediated Neurotoxicity.

OBJECTIVE: The objective of this study is to investigate the neuroprotective effects of ß- sitosterol using the AlCl3 model of Alzheimer's Disease. METHODS: AlCl3 model was used to study cognition decline and behavioral impairments in C57BL/6 mice. Animals were randomly assigned into 4 groups with the following treatments: Group 1 received normal saline for 21 days, Group 2 received AlCl3 (10 mg/kg) for 14 days; Group 3 received AlCl3(10 mg/kg) for 14 days + ß-sitosterol (25mg/kg) for 21 days; while Group 4 was administered ß-sitosterol (25mg/kg) for 21 days. On day 22, we performed the behavioral studies using a Y maze, passive avoidance test, and novel object recognition test for all groups. Then the mice were sacrificed. The corticohippocampal region of the brain was isolated for acetylcholinesterase (AChE), acetylcholine (ACh), and GSH estimation. We conducted histopathological studies using Congo red staining to measure ß -amyloid deposition in the cortex and hippocampal region for all animal groups. RESULTS: AlCl3 successfully induced cognitive decline in mice following a 14-day induction period, as shown by significantly decreased (p < 0.001) in step-through latency, % alterations, and preference index values. These animals also exhibited a substantial decrease in ACh (p <0.001) and GSH (p < 0.001) and a rise in AChE (p < 0.001) compared to the control group. Mice administered with AlCl3 and ß-sitosterol showed significantly higher step-through latency time, % alteration time, and % preference index (p < 0.001) and higher levels of ACh, GSH, and lower levels of AChE in comparison to the AlCl3 model. AlCl3-administered animals also showed higher ß-amyloid deposition, which got significantly reduced in the ß-sitosterol treated group. CONCLUSION: AlCl3 was effectively employed to induce a cognitive deficit in mice, resulting in neurochemical changes and cognitive decline. ß -sitosterol treatment mitigated AlCl3-mediated cognitive impairment.

Contact Allergy to Two Aluminum Salts in Consecutively Patch-Tested Dermatitis Patients.

BACKGROUND: Recently, aluminum chloride hexahydrate (ACH) 10.0% petrolatum (pet) was recommended for patch testing to detect aluminum contact allergy. Aluminum lactate (AL) may be as reliable a test substance as ACH. OBJECTIVE: We aimed to investigate the frequencies of aluminum allergy when ACH and AL were used in patch testing consecutive patients. METHODS: Petrolatum preparations of ACH 10.0% and AL 12.0% were added to the baseline series in 2010-2017. Aluminum chloride hexahydrate 10.0% pet was added to the children baseline series from July 1, 2012, to December 31, 2017. RESULTS: A total of 5448 patients were patch tested with the extended baseline series and 196 children with the extended children baseline series. Forty-eight of the 5448 adults (0.9%) and 10 of the 196 children (5.1%) were diagnosed with aluminum contact allergy. A significant difference was found between the aluminum allergy frequencies in children and adults patch tested with ACH in 2013-2017 (P < 0.001). The difference between the frequencies of contact allergies for the 2 aluminum salts is not statistically significant. CONCLUSIONS: Patch testing with ACH and AL demonstrated similar contact allergy frequencies. To detect aluminum allergy, patch testing with ACH 10.0% pet is recommended. Aluminum chloride hexahydrate 10.0% pet should be considered for inclusion in baseline series for patch testing adults and children.

Investigation of TNFα Level and Metallothionein Gene Expression in Livers of Rats Exposed to Dietary Aluminum.

Aluminum chloride is a chemical compound widely used in both pharmaceutical and industrial sectors. The present study aimed to assess the effect of aluminum chloride on TNF levels and metallothionein gene expression in rat livers. A total of 16 Wistar rats were used as an experimental model and assigned to four groups (n=4). The treated groups received aluminum chloride (Sigma/USA) at a dose of 25g/kg body weight via a feeding tube as follows: group 1: Non-treated rats as the control group, group 2 were treated with aluminum chloride for 8 weeks, group 3 were treated with aluminum chloride for 12 weeks, and group 4 received aluminum chloride for 16 weeks. The TNF-α was measured in liver tissue using an enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry and real-time polymerase chain reaction (RT-PCR) were used to analyze metallothionein gene expression in rat liver. To estimate TNF levels, the results revealed that levels were considerably higher (P<0.01) in all experimental groups, especially in group 4 which underwent treatment for 16 weeks (401±22.1 ng/ml), as compared to that in the control group. For the immunohistochemistry assay, a gradient intensity of staining for liver tissue was observed, ranging from zero staining in the control group to moderate, medium, and high staining in the experimental groups after 8, 12, and 16 weeks of aluminum chloride treatment, respectively. The greatest amount of methylothionine expression was observed in the livers of group 4 which received aluminum chloride for 16 weeks (15.5-fold), with a significant difference (P<0.01) from the other experimental groups. In both immunohistochemical and RT-PCR experiments, aluminum administration had a substantial influence on TNFα levels and metallothionein expression in rat livers.

Physiology-based toxicokinetic modelling of aluminium in rat and man.

A sufficient quantitative understanding of aluminium (Al) toxicokinetics (TK) in man is still lacking, although highly desirable for risk assessment of Al exposure. Baseline exposure and the risk of contamination severely limit the feasibility of TK studies administering the naturally occurring isotope 27Al, both in animals and man. These limitations are absent in studies with 26Al as a tracer, but tissue data are limited to animal studies. A TK model capable of inter-species translation to make valid predictions of Al levels in humans-especially in toxicological relevant tissues like bone and brain-is urgently needed. Here, we present: (i) a curated dataset which comprises all eligible studies with single doses of 26Al tracer administered as citrate or chloride salts orally and/or intravenously to rats and humans, including ultra-long-term kinetic profiles for plasma, blood, liver, spleen, muscle, bone, brain, kidney, and urine up to 150 weeks; and (ii) the development of a physiology-based (PB) model for Al TK after intravenous and oral administration of aqueous Al citrate and Al chloride solutions in rats and humans. Based on the comprehensive curated 26Al dataset, we estimated substance-dependent parameters within a non-linear mixed-effect modelling context. The model fitted the heterogeneous 26Al data very well and was successfully validated against datasets in rats and humans. The presented PBTK model for Al, based on the most extensive and diverse dataset of Al exposure to date, constitutes a major advancement in the field, thereby paving the way towards a more quantitative risk assessment in humans.

Curcumin Attenuated Neurotoxicity in Sporadic Animal Model of Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases leading to dementia. Despite research efforts, currently there are no effective pharmacotherapeutic options for the prevention and treatment of AD. Recently, numerous studies highlighted the beneficial effects of curcumin (CUR), a natural polyphenol, in the neuroprotection. Especially, its dual antioxidant and anti-inflammatory properties attracted the interest of researchers. In fact, besides its antioxidant and anti-inflammatory properties, this biomolecule is not degraded in the intestinal tract. Additionally, CUR is able to cross the blood-brain barrier and could therefore to be used to treat neurodegenerative pathologies associated with oxidative stress, inflammation and apoptosis. The present study aimed to assess the ability of CUR to induce neuronal protective and/or recovery effects on a rat model of neurotoxicity induced by aluminum chloride (AlCl3), which mimics the sporadic form of Alzheimer's disease. Our results showed that treatment with CUR enhances pro-oxidant levels, antioxidant enzymes activities and anti-inflammatory cytokine production and decreases apoptotic cells in AlCl3-exposed hippocampus rats. Additionally, histopathological analysis of hippocampus revealed the potential of CUR in decreasing the hallmarks in the AlCl3-induced AD. We also showed that CUR post-treatment significantly improved the behavioral, oxidative stress and inflammation in AlCl3-exposed rats. Taken together, our data presented CUR as a nutraceutical potential through its protective effects that are more interesting than recovery ones in sporadic model of AD.

Oral exposure to aluminum leads to reduced nicotinic acetylcholine receptor gene expression, severe neurodegeneration and impaired hippocampus dependent learning in mice.

Aluminum (Al) is known for its neurotoxicity for over a century and is reported to have specifically high toxicity for cholinergic system. The effect of Al on muscarinic acetylcholine receptors is widely reported, but its effect on nicotinic acetylcholine receptors (nAChRs) is less well known. The aim of this study was to determine the effects of Al on hippocampus dependent learning and memory, function and expression of nAChRs in the hippocampus. Al concentration and neurodegeneration were also measured in the hippocampus following Al treatment. The mice were treated with 250 mg/kg AlCl3.6H2O in drinking water for a period of 42 days. Results show that Al treated animals have significantly reduced spatial reference memory as compared to control animals in Morris water maze test. Similarly, Al treated animals showed reduced contextual memory for Pavlovian fear compared to control animals. Al treated animals show higher anxiety in elevated plus maze as compared to control animals. The analysis of nAChR expression via RT-PCR showed reduced expression of α7, α4 and ß2 nAChR gene expression in the hippocampus of Al treated animals. High Al accumulation was observed in Al-treated animals (688.14 ± 242.82 µg/g) compared to the control group (115.14 ± 18.18 µg/g) that resulted in severe neurodegeneration in the hippocampus. These results demonstrated that Al exposure caused neurotoxicity in mice hippocampus which is manifested by reduced memory and elevated anxiety. The results were further validated by high Al accumulation in the hippocampus, severe neurodegeneration and reduced expression of nAChRs.

Pomegranate juice rescues developmental, neurobehavioral and biochemical disorders in aluminum chloride-treated male mice.

PURPOSE: Aluminum (Al) is a harmful metal to organisms and is capable of entering the human body in multiple ways, such as through drinking, breathing, deodorant use, and vaccination. This study examined the prospective toxicity of Al and the protective attributes of pomegranate juice (PJ) on neurobehavioral and biochemical parameters of male mice. METHODS: Six groups of male mice were treated for 35 days with 20 % PJ (group II), 40 % PJ (group III), 400 mg/kg Al (group IV), Al + 20 % PJ (group V), Al + 40 % PJ (group VI) or tap water (control, group I). Behavioral assessments were conducted for learning and memory evaluations at the end of experiment. In addition, the forebrain was isolated for biochemical analysis. RESULTS: The exposure of male mice to Al decreased learning and memory retention in the shuttle box, Morris water-maze and T-Maze tests. Biochemical analysis revealed significant depletions in neurotransmitters including DA, 5-HT and AChE and oxidative proteins including GSH, GST, CAT and SOD and increased TBARES levels in Al-treated mice compared to untreated mice. Pomegranate juice provided protection against these effects after Al exposure by ameliorating learning and memory retention and oxidative state in a dose-independent manner. CONCLUSION: Our data demonstrated that Al exposure caused behavioral and biochemical disorders. Pomegranate juice in lower dose has beneficial properties for health and can be used as a source of antioxidants to reduce the toxicity of Al and other substances.

A Novel Nanoformulation of Ellagic Acid is Promising in Restoring Oxidative Homeostasis in Rat Brains with Alzheimer's Disease.

BACKGROUND: Aluminum toxicity induces neurodegenerative changes in the brain and results in Alzheimer's disease (AD). OBJECTIVE: Here, the aim was to evaluate the antioxidant therapeutic effects of ellagic acid (EA) and EA-loaded nanoparticles (EA-NP) in an aluminum chloride-induced AD rat model. METHODS: The nanoparticles' loading of EA was 0.84/1 w/w. The in vitro release kinetics of EA from EA-NP in fetal bovine serum showed 60% release in the first 1-5 hours, followed by sustained release at 60-70% over 6-24 hours. Six groups were implemented; group 1 served as the control, group 2 received EA, group 3 received EA-NP, group 4 was the AD rat model administered AlCl3 (50 mg/kg) for 4 weeks, groups 5 (AD+EA) and 6 (AD+EA-NP) were treated with EA and EA-NP, respectively, for 2 weeks after AlCl3 was stopped. The neurotoxicity in the rat brain was examined by measuring the brain antioxidant biomarkers catalase, glutathione, and total antioxidant activity and lipid peroxidation (thiobarbituric acid, TBA). Histopathological studies using hematoxylin and eosin, cresyl violet, silver stains, and the novel object recognition test were examined. RESULTS: Data revealed significant increase of antioxidant biomarkers and decreased TBA in the EA-NP group. The pathological hallmarks of AD-vacuolation of the neurons, chromatolysis, neurofibrillary tangles, and the senile plaques in brains of the AD rat model were decreased and restoration of Nissl granules was noted. The calculated discrimination index in the behavioral test increased more in cases treated with EA-NP. CONCLUSION: The treatment of AD with EA-NP was more effective than EA in alleviating the oxidative neurotoxic effects on AD rat brains.

Preclinical evidences of aluminum-induced neurotoxicity in hippocampus and pre-frontal cortex of rats exposed to low doses.

Aluminum (Al) is a neurotoxicant agent implicated in several behavioral, neuropathological and neurochemical changes associated with cognitive impairments. Nevertheless, mechanisms of damage and safety concentrations are still very discussed. Thus, the main purpose of this study was to investigate whether two aluminum low doses were able to produce deleterious effects on cognition of adult rats, including oxidative stress in hippocampus and prefrontal cortex, two important areas for cognition. For this, thirty adult Wistar rats were divided into three groups: Al1 (8.3 mg/kg/day), Al2 (32 mg/kg/day) and Control (Ultrapure Water), in which all three groups received their solutions containing or not AlCl3 by intragastric gavage for 60 days. After the experimental period, the short- and long-term memories were assessed by the object recognition test and step-down inhibitory avoidance. After euthanizing, prefrontal cortex and hippocampus samples were dissected for Al levels measurement and evaluation of oxidative biochemistry. Only Al2 increased Al levels in hippocampal parenchyma significantly; both concentrations did not impair short-term memory, while long-term memory was affected in Al1 and Al2. In addition, oxidative stress was observed in prefrontal and hippocampus in Al1 and Al2. Our results indicate that, in a translational perspective, humans are subjected to deleterious effects of Al over cognition even when exposed to low concentrations, by triggering oxidative stress and poor long-term memory performance.

ATR-IR and EPR spectroscopy for following the membrane restoration of isolated cortical synaptosomes in aluminium-induced Alzheimer's disease - Like rat model.

Synaptosomal membrane peroxidation and alteration in its biophysical properties are associated with Aluminium (Al) toxicity that may lead to cognitive dysfunction and Alzheimer's disease (AD) like pathogenesis. Here we investigated the therapeutic potential of Lepedium sativum (LS) as a natural anti-inflammatory, antioxidant and as acetyl cholinesterase inhibitor in treating Al induced AD-like in rat model. We utilized ATR-IR spectroscopy to follow the restoration in the damaged membrane structure of isolated rat cortical synaptosomes and its biophysical properties, electron paramagnetic resonance (EPR) spin trapping to follow NADPH oxidase activity (NOX), and EPR spin labelling in response to LS treatment after Al intoxication. We measured the concentration of Ca2+ ions in rat cortical tissue by inductively coupled plasma (ICP), the brain atrophy/curing and hydrocephalus by magnetic resonance imaging (MRI) besides light microscope histopathology. Our results revealed significant increase in synaptosomal membrane rgidification, order, lipid packing, reactive oxygen species (ROS) production and Ca2+ ion concentration as a result of Al intoxication. The dramatic increase in Ca2+ ion concentration detected in AD group associated with the increase in synaptic membrane polarity and EPR-detected order S-parameter suggest that release of synaptic vesicles into synaptic cleft might be hindered. LS treatment reversed these changes in synaptic membranes, and rescued an observed deficit in the exploratory behaviour of AD group. Our results also strongly suggest that the synaptosomal membrane phospholipids that underwent free radical attacks mediated by AlCl3, due to greater NOX activity, was prevented in the LS group. The results of ATR-IR and EPR spectroscopic techniques recommend LS as a promising therapeutic agent against synaptic membrane alterations opening a new window for AD drug developers.

Effect of moringa oleifera lam. leaf extract against aluminium chloride induced hippocampal histology and serum enzyme activities in adult Wistar rats / Efecto del extracto de hoja de Moringa Olifera Lam. en la histología del hipocampo y la actividad enzimática en el suero de ratas Wistar adultas expuestas a cloruro de aluminio

Introduction: Aluminium, a ubiquitous metal implicated in some neurodegenerative diseases is linked to activation of free oxygen species. The antioxidant-rich plants, Moringa oleifera (MO) is reported to protect against Aluminium activities. This study investigated the actions of MO leaf extract (MOLE) against Aluminium chloride (AlCl3)- induced hippocampal cellular changes and serum levels of alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT) in adult Wistar rats.Materials and Methods: Thirty Wistar rats weighing between 150 g and 220 g were grouped (n=5) into; 1-control (5 mL/kg distilled water), 2-AlCl3 (100 mg/kg), 3-low dose MOLE (250 mg/kg), 4-high dose MOLE (1,000 mg/kg), 5-concurrent AlCl3 and low dose MOLE, and 6-concurrent AlCl3 and high dose MOLE. All administrations were by oral gavages for 21 days. On day 22, following deep anaesthesia and cardiac puncture, blood was obtained for serum enzyme analysis, and the brain perfusion fixed, harvested and processed for histological study.Results: Results showed significantly (p < 0.05) higher ALP level in the AlCl3 group compared with the control, as well as the other test groups. However, there was no significant (p > 0.05) AST and ALT levels. The hippocampal CA3 of the AlCl3 group showed hypertrophic cells, with some of the cells having karyorrhectic features. The concurrent AlCl3 and low and high doses, MOLE groups showed less of these adverse features.Conclusion: These results suggest that MOLE may protect enzymatic activities against Aluminium chloride. However, its action on hippocampus is still subject to further investigation.

Introducción: El aluminio, un metal presente en diversos lugares implicado en algunas enfermedades neurodegenerativas, está relacionado con la activación de especies reactivas de oxígeno. Se informa que las plantas ricas en antioxidantes, Moringa oleifera (MO) protegen contra la acción del aluminio. Este estudio investigó las acciones del extracto de hoja de MO (MOLE) en los cambios celulares del hipocampo inducidos por el cloruro de aluminio (AlCl3) y los niveles séricos de fosfatasa alcalina (ALP), aspartato transaminasa (AST) y alanina transaminasa (ALT) en ratas Wistar adultas.Materiales y métodos: SE utilizaron treinta ratas Wistar divididas en 5 grupos, los animales pesaban entre 150 gy 220 g; 1 control (5 ml / kg de agua destilada), 2-AlCl3 (100 mg / kg), 3 MOLE de dosis baja (250 mg / kg), 4 MOLE de dosis alta (1000 mg / kg), 5 AlCl3 concurrente y MOLE de dosis baja, y MOLE 6-concurrente y MOLE de dosis alta. Todas las administraciones fueron por sonda oral durante 21 días. El día 22, después de la anestesia profunda y la punción cardíaca, se obtuvo sangre para el análisis de las enzimas séricas y la perfusión cerebral se fijó, recogió y procesó para el estudio histológico.Resultados: Los resultados mostraron un nivel de ALP significativamente (p <0.05) más alto en el grupo AlCl3 en comparación con el control, así como en los otros grupos de prueba. Sin embargo, no hubo niveles significativos (p> 0.05) de AST y ALT. El hipocampo CA3 del grupo AlCl3 mostró células hipertróficas, y algunas de las células tenían características cariorrecticas. Los grupos de AlCl3 concurrentes y dosis bajas y altas, MOLE mostraron menos de estas características adversas.Conclusión: Estos resultados sugieren que MOLE puede proteger las actividades enzimáticas contra el cloruro de aluminio. Sin embargo, su acción sobre el hipocampo aún está sujeta a más investigaciones.

Ginsenoside Rg1 ameliorates the cognitive deficits in D-galactose and AlCl3-induced aging mice by restoring FGF2-Akt and BDNF-TrkB signaling axis to inhibit apoptosis.

Ginsenoside Rg1 is the main active ingredient of Panax ginseng with the activity of neuroprotective, antioxidant and strengthening the immune system. Therefore, we hypothesized that Rg1 may afford anti-aging effects although the mechanism remains to be elucidated. In this study, chemically induced aging mice were established by consecutive administration of D-galactose and AlCl3. We found that Rg1 effectively ameliorates spatial learning and memory deficits in aging mice demonstrated by their improved performance in step down avoidance tests and Morris water maze experiments. Rg1 restored aging-induced decline of FGF2 and BDNF, reactivated TrkB/Akt signaling pathways in the hippocampus and prefrontal cortex to inhibit apoptosis, for the expression of anti-apoptotic protein Bcl-2 and apoptosis promoting enzyme cleaved-Caspase3 were antagonistically restored. Therefore, these results established the anti-aging effects of Rg1, and FGF2, BDNF and associated signaling pathways might be promising targets. Our data may provide a new avenue to the pharmacological research and diet therapeutic role of ethnic products such as Rg1 in anti-aging and aging associated diseases.

Combined effect of silver nanoparticles and aluminium chloride, butylparaben or diethylphthalate on the malignancy of MDA-MB-231 breast cancer cells and tumor-specific immune responses of human macrophages and monocyte-derived dendritic cells.

The aim of this study was to assess whether silver nanoparticles (AgNP) or selected cosmetic ingredients may modify functions of various immunocompetent cell populations. To this end, the effect of two AgNP (size of 15 nm or 45 nm), alone and in combination with aluminium chloride, butyl paraben, di-n-butyl phthalate or diethyl phthalate was assessed on: (1) migration and invasion of MDA-MB-231 human breast cancer cells; (2) M1/M2 polarization of phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophages (M0) and (3) activation/maturation of monocyte-derived dendritic cells (DCs). The results of this study showed that neither any of the test chemicals alone nor the mixtures significantly changed the migration or invasion ability of MDA-MB-231 cells following, both 72-h and 21-day exposure. Analysis of the expression of marker genes for both M1 (IL-1B, CXCL9, TNF) and M2 (DCSIGN, MRC1) polarization revealed that the chemicals/mixtures did not activate M1/M2 differentiation of the M0 macrophages. In addition, no significant changes were observed in the expression of CD86, HLA-DR and CD54 surface markers and phagocytic activity of DCs following 48-h exposure to AgNP alone or in combination with test compounds. Our study suggests that AgNP alone or in combination with tested cosmetic ingredients do not alter function of immunocompetent cells studied.

Combination of cyclodextrin complexation and iontophoresis as a promising strategy for the cutaneous delivery of aluminum-chloride phthalocyanine in photodynamic therapy.

Topical application of aluminum-chloride phthalocyanine (AlClPc) is a challenge because of the drug's extremely low solubility, which prevents its absorption into deeper skin layers and causes molecule aggregation, reducing the photophysical effect. The goal of this study was to obtain a formulation applied in a certain condition that would allow homogeneous accumulation of AlClPc in cutaneous tissues, meaning a safer and non-invasive topical treatment for skin tumors based on photodynamic therapy. We first prepared and characterized AlClPc complexes with cyclodextrin to increase the photosensitizing agent solubility. The inclusion complex of AlClPc with hydroxypropyl-ß-cyclodextrin (HP-ßCD) amplified its loading dose in aqueous medium and maintained its photosensitizing properties in terms of reactive oxygen species production. Assays to determine the complex's in vitro cytotoxicity against murine melanoma skin cancer cells showed that when irradiated, the complex significantly reduced cell viability, whereas the absence of irradiation did not affect cell viability. Three physical techniques for permeation enhancement (i.e., tape-stripping abrasion, microneedle pretreatment and iontophoresis) were then evaluated. When applied in impaired skin, the complex could not increase drug penetration. The skin penetration of AlClPc, however, increased 2.3-fold following iontophoresis application in a shorter period compared to passive permeation. Therefore, these results suggest the administration of complexed AlClPc mediated by iontophoresis, followed by application of photodynamic therapy, might be an effective and non-invasive alternative for topical treatment of cutaneous tumors.

Ocular Chemical burns in the dermatology office: a practical approach to managing safety precautions.

Chemical burns to the eyes are one of the few ocular emergencies that dermatologists may encounter in their everyday clinic. As such, dermatologists should be confident in their ability to urgently manage ocular chemical injuries should accidental exposure occur during a procedure. We report a case of accidental ocular exposure to aluminum chloride hexahydrate during skin biopsy of the cheek and subsequent transient ocular injury that resolved with early appropriate management. This article provides background information on acute chemical ocular injuries, offers practical step-by-step guidance for the dermatologist, and highlights immediate copious irrigation as perhaps the most critical step in determining the clinical course of the injury.

Patch testing children with aluminium chloride hexahydrate in petrolatum: A review and a recommendation.

BACKGROUND: According to studies on adults, patch testing with aluminium chloride hexahydrate 2% pet. is insufficient to detect aluminium allergy, and a 10% preparation is recommended. Other studies suggest that a 2% preparation is sufficient for testing children. OBJECTIVES: To review three previously published Swedish studies on patch testing children with aluminium chloride hexahydrate 2% pet. PATIENTS/METHODS: Altogether, 601 children with persistent itching subcutaneous nodules (granulomas) induced by aluminium-adsorbed vaccines were patch tested with aluminium chloride hexahydrate 2% pet. and metallic aluminium in (a) a pertussis vaccine trial, (b) clinical practice, and (c) a prospective study. RESULTS: Overall, 459 children had positive reactions to the 2% pet. preparation. Another 10 reacted positively only to metallic aluminium. An extreme positive reaction (+++) was seen in 65% of children aged 1 to 2 years as compared with 22% of children aged 7 years. From 8 years onwards, extreme positive reactions were scarce. CONCLUSIONS: Aluminium chloride hexahydrate 2% pet. is sufficient to trace aluminium allergy in children. Small children are at risk of extreme reactions. We thus suggest that aluminium chloride hexahydrate 10% pet. should not be used routinely in children before the age of 7 to 8 years.

An aluminum adjuvant-integrated nano-MOF as antigen delivery system to induce strong humoral and cellular immune responses.

Metal-organic frameworks (MOFs) have high surface area, tunable pore size, and high loading capacity, making them promising for drug delivery. However, their synthesis requires organic solvents, high temperature and high pressure that are incompatible with biomacromolecules. Zeolitic imidazole frameworks (ZIF-8) which forms through coordination between zinc ions and 2-methylimidazole (MeIM) have emerged as an advanced functional material for drug delivery due to its unique features such as high loading and pH-sensitive degradation. In this study, we took advantage of a natural biomineralization process to create aluminum-containing nanoZIF-8 particles for antigen delivery. Without organic solvents or stabilizing agent, nanoparticles (ZANPs) were synthesized by a mild and facile method with aluminum, model antigen ovalbumin (OVA) and ZIF-8 integrated. A high antigen loading capacity (%) of 30.6% and a pH dependent antigen release were achieved. A Toll-like receptor 9 agonist cytosine-phosphate-guanine oligodeoxynucleotides (CpG) was adsorbed on the surface of ZANPs (hereafter CpG/ZANPs) to boost the immune response. After subcutaneous injection in vivo, CpG/ZANPs targeted lymph nodes (LNs), where their cargo was efficiently internalized by LN-resident antigen-presenting cells (APCs). ZANPs decomposition in lysosomes released antigen into the cytoplasm and enhanced cross-presentation. Moreover, CpG/ZANPs induced strong antigen-specific humoral and cytotoxic T lymphocyte responses that significantly inhibited the growth of EG7-OVA tumors while showing minimal cytotoxicity. We demonstrate that ZANPs may be a safe and effective vehicle for the development of cancer vaccines.

Aluminum Chloride versus Electrocauterization in Periapical Surgery: A Randomized Controlled Trial.

INTRODUCTION: The aim of this study was to evaluate the efficacy of 2 hemostatic agents in periapical surgery and its relationship with patient- and tooth-dependent variables. METHODS: A prospective study was designed with 2 randomized parallel groups established according to the hemostatic agent used: aluminum chloride or electrocauterization. The surgeon and 2 independent blinded observers examined the initial and final bleeding and recorded it as 0 (no hemorrhage control), 1 (slight but apparent intermittent bleeding), or 2 (complete hemorrhage control). The following patient- and tooth-dependent variables were collected: sex, age, smoking habit, plaque index, and position. RESULTS: Sixty patients with a periapical lesion in the esthetic zone were enrolled in this study and divided into 2 groups of 30 patients. In the aluminum chloride group, complete hemorrhage control was achieved in 24 patients, and in the electrocauterization group, it was achieved in 18 patients (P < .05). A relationship between sex and the effectiveness of hemostasis was found; a female patient increases the possibility of achieving complete hemorrhage control. CONCLUSIONS: Hemorrhage control was better in the aluminum chloride group than in the electrocauterization group as well as in female patients compared with male patients.

Protective effect of raisin (currant) against spatial memory impairment and oxidative stress in Alzheimer disease model.

Objectives: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive pathological changes of the brain. A number of studies demonstrated compelling evidence of the importance of oxidative processes in AD pathogenesis. Raisin contains polyphenol, phenolic acid, and tannin compounds, which have antioxidant and anti-inflammatory properties. The present study was aimed to evaluate the protective effect of raisin on neurobehavioral and histological changes in rats with Alzheimer. Methods: Animal model of AD was induced by intraperitoneal injection of aluminium chloride for 60 days (100 mg/kg body weight). During these 60 days both Alzheimer's and control rats were given 6 g of raisin per rat. At the end of the treatment, blood was collected for biochemical assessment. We used a Morris water task and passive avoidance test to assess spatial memory. Results: Our results showed that aluminium exposure significantly decreased the memory in the MWT and passive avoidance test, but in the raisin + AlCl3 group, it significantly increased spatial memory in both tests. Also, Aluminium exposure significantly increased malondialdehyde (MDA) and decreased ferric reducing ability of plasma (ferric reducing/antioxidant power (FRAP)), while treatment with raisin significantly decreased MDA and increased FRAP in plasma of blood. Discussion: Our findings showed that raisin has a neuroprotective effect and improves the spatial memory in AD animal models.