Aluminum-Allergen of the Year 2022.

ABSTRACT: Exposure to elemental aluminum and its salts is unavoidable. Aluminum as a metal is present in transport, construction, packaging, and electronic equipment. Aluminum salts are present in consumer products, food items and drinking water, vaccines, drugs, and antiperspirants. Aluminum in vaccines and preparations for allergen-specific immunotherapy are the major sensitization sources. The predominent clinical manifestations of aluminum allergy are pruritic subcutaneous nodules and eczematous dermatitis. Patch testing shall be performed with aluminum chloride hexahydrate (ACH) in petrolatum. The preparation with ACH 10% detects substantially more aluminum allergy than ACH 2%. A patch test with elemental aluminum, for example, an empty Finn Chamber, is only positive when there is a strong aluminum allergy. A patch test reading should be performed 1 week after the application so as not to miss 15% to 20% of aluminum allergy. Aluminum should be included in any baseline patch test series for children and investigated for a possible inclusion in baseline series for adults. Aluminum test chambers can interfere with the testing resulting in both false-negative and false-positive patch test reactions to nonaluminum contact sensitizers.

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.

A Reduced Dose Whole Virion Aluminum Adjuvanted Seasonal Influenza Vaccine Is Immunogenic, Safe, and Well Tolerated in Pediatric Patients.

BACKGROUND: Data suggest that pediatric patients might react differently to influenza vaccination, both in terms of immunity and side effects. We have recently shown that using a whole virion vaccine with aluminum phosphate adjuvants, reduced dose vaccines containing 6 µg of viral hemagglutinin (HA) per strain are immunogenic, and well tolerated in adult and elderly patients. Here we show the results of a multicenter clinical trial of pediatric patients, using reduced doses of a new, whole virion, aluminum phosphate adjuvanted vaccine (FluArt, Budapest, Hungary). METHODS: A total of 120 healthy volunteers were included in two age groups (3-11 years, receiving 3 µg of HA per strain, and 12-18 years, receiving 6 µg of HA per strain). We used hemagglutination inhibition testing to assess immunogenicity, based on EMA and FDA licensing criteria, including post/pre-vaccination geometric mean titer ratios, seroconversion and seropositivity rates. Safety and tolerability were assessed using CHMP guidelines. RESULTS: All subjects entered the study and were vaccinated (ITT population). All 120 subjects attended the control visit on Day 21 (PP population). All immunogenicity licensing criteria were met in both age groups for all three vaccine virus strains. No serious adverse events were detected and the vaccine was well tolerated by both age groups. DISCUSSION: Using a whole virion vaccine and aluminum phosphate adjuvants, a reduction in the amount of the viral hemmaglutinin is possible while maintaining immunogenicity, safety and tolerability in pediatric and adolescent patients.

Association between aluminum in drinking water and incident Alzheimer's disease in the Canadian Study of Health and Aging cohort.

Epidemiological evidence linking aluminum in drinking water and Alzheimer's disease (AD) has been inconsistent, with previous studies often limited by small sample sizes. The present study addresses this issue using data from the Canadian Study of Health and Aging (CSHA), a prospective cohort of 10,263 subjects followed-up from 1991-1992 through 2001-2002. Participants' residential histories were linked to municipal drinking water sources in 35 Canadian municipalities to obtain ecologic pH, aluminum, fluoride, iron and silica concentrations in drinking water. Cox proportional hazards models were used to examine associations between aluminum and incident AD [Hazard Ratios (HRs), 95% confidence intervals (CIs)], adjusting for age, gender, history of stroke, education, and high blood pressure. A total of 240 incident AD cases were identified during follow-up of 3, 638 subjects derived from the CSHA cohort with complete data on all covariates. With categorical aluminum measurements, there was an increasing, but not statistically significant, exposure-response relationship (HR = 1.34, 95% CI 0.88-2.04, in the highest aluminum exposure category; p = 0.13 for linear trend). Similar results were observed using continuous aluminum measurements (HR=1.21, 95% CI 0.97-1.52, at the interquartile range of 333.8 µg/L; p = 0.09 for linear trend). In a subsample genotyped for ApoE-ε4, there was some evidence of an association between aluminum and AD (p = 0.03 for linear trend). Although a clear association between aluminum in drinking water and AD was not found, the linear trend observed in ApoE-ε4 subsample warrants further examination.

Efficacy and tolerability of 20% aluminum sesquichlorohydrate vs 20% aluminum chloride for the treatment of axillary hyperhidrosis: A randomized controlled trial.

This study evaluated the efficacy and tolerability of topical aluminum sesquichlorohydrate (AS) when compared to aluminum chloride (AC) as a treatment for primary axillary hyperhidrosis (PAH). Twenty subjects were included in this randomized, controlled, split-side 8-week study. All participants applied 20% AS and 20% AC lotions in their axillae (one treatment per axilla) every night for 2 weeks; next, the application was reduced to three times a week for 4 weeks. The assessment was performed using the sweating intensity visual scale (SIVS), hyperhidrosis disease severity score (HDSS), patient satisfaction score, and the appearance of adverse effects on weeks 0, 1, 2, 4, 6, and 8. Both AS as well as AC application showed positive results, significantly differing from the baseline, as assessed using SIVS, HDSS, and patient satisfaction score at every follow-up visit; however, no significant difference was observed between the AS and AC groups at any follow-up visit. The mean time of response was 1.14 weeks for both treatments. A side effect was observed in one subject (5%), who reported itching on the AC axilla. The therapeutic effects persisted even after reducing the frequency of application and lasted for at least 2 weeks after cessation of use. In conclusion, topical 20% AS demonstrated similar efficacy to topical 20% AC in the treatment of PAH, with a high safety profile.

Fish Oil and Primrose Oil Suppress the Progression of Alzheimer's Like Disease Induced by Aluminum in Rats.

The role of fish oil, primrose oil and their mixture in ameliorating the changes in Alzheimer's like model was evaluated in rats. Primrose oil and primrose/fish oil mixture fatty acids composition was assessed by gas chromatography. The rat experiment consisted of 5 groups; the first fed on balanced diet as control normal (CN); the other four groups treated with intraperitoneal aluminum lactate and consumed dyslipidemic diet; one group served as control Alzheimer's like disease (CA) while the other three groups (test groups) received daily oral dose from primrose oil, fish oil and primrose/fish oil mixture separately for 5 weeks. Results showed primrose oil and primrose/ fish oil mixture to contain gamma linolenic acid as 9.15 and 4.3% of total fatty acids, respectively. Eicosapentaenoic and docosahexaenoic were present as 10.9 and 6.5 %, respectively in the oil mixture. Dyslipidemia and increased erythrocyte sedimentation rate (ESR), plasma butyrylcholinesterase (BChE), brain malondialdehyde (MDA) and NO with decrease in plasma magnesium, brain catalase, reduced glutathione, body weight gain and brain weight were demonstrated in CA compared to CN. Brain histopathology and immuno-histochemistry showed neuronal degeneration and neurofibrillary tangles with elevated myeloperoxidase and nuclear factor-kappa B in CA compared to CN. The tested oils demonstrated neuro-protection reflected in the variable significant improvement of biochemical parameters, immuno-histochemistry and brain histopathology. Primrose/fish oil mixture was superior in reducing ESR, brain MDA, plasma activity of BChE and brain histopathological changes along with elevating plasma magnesium. Primrose/fish oil mixture and fish oil were more promising in improving plasma high density lipoprotein cholesterol (HDL-C) than primrose. Fish oil was the most efficient in improving plasma total cholesterol (T-C), low density lipoprotein cholesterol and T-C /HDL-C. Primrose/fish oil mixture and primrose oil were superior in elevating brain catalase compared to fish oil. Other parameters were equally improved by the different oil treatments. Primrose oil, fish oil and their mixture reduced the progression of Alzheimer's disease in rats with superiority to primrose/fish oil mixture.

Neuro-amelioration of cinnamaldehyde in aluminum-induced Alzheimer's disease rat model.

Aluminum (Al) is a neurotoxic substance which has played an important role in the etiology, pathogenesis, and development of amyloid-ß (Aß) plaques. This study was carried out to evaluate the neuroprotective effect of aqueous cinnamon extract against aluminum chloride (AlCl3)-induced Alzheimer's disease. Forty adult male albino rats, randomly divided into four equal groups. Control group; ACE200 group administered aqueous cinnamon extract (ACE) orally; AlCl3 group received daily intraperitoneal (i.p.) injection of AlCl3 for 60 days to induce neurotoxicity and AlCl3 + ACE200 group received a combination of AlCl3 and ACE in the same dose and route as previous groups. Aluminum administration significantly enhanced the memory impairment and the Aß formation in the rat model. The cerebellum exhibited a significant reduced number of Purkinje cells, marked decrease in the density of dendritic arborization and prominent perineuronal spaces in the molecular layer. There was loss of dendritic spines, neurofibrillary degeneration, and appearance of neuritic plaques. Concomitant administration of AlCl3 and ACE displayed an observable protection against these changes with progressive improvement in memory and intellectual performance. In conclusion, ACE may play a protective role against formation of amyloid-ß plaques in cerebellum.

Reactogenicity of Bordetella pertussis vaccines formulations using aluminum adjuvants in Sprague Dawley rats / Reactogenicidad de formulaciones de vacunas de Bordetella pertussis utilizando adyuvantes de aluminio en ratas Sprague Dawley

Combined vaccines for childhood are a strategy in the prevention of several diseases. These can maximize protection and decrease immunization schedules in children. New candidates are getting closer to being able to meet these needs, but they raise numerous strategic questions related to formulation and regulatory aspects. In addition to being immunogenic and protective must have low reactogenicity when combined with other antigens. Adjuvants are important components in achieving these combinations. Therefore, a reactogenicity study was designed for two Bordetella pertussis formulations containing hydroxide or aluminum phosphate in Sprague Dawley rats. Both formulations dose were administered in 0.2 mL intramuscularly. Clinical evaluations, body weight, water consumption, food, temperature, muscle volume, dermal irritability and pathological studies with special interest at the inoculation site were carried out. Only differences in body temperature and muscle volume were found with a slight increase in values with return to normal. The macroscopic study showed lesions at the site of inoculation, consid­ered characteristics of aluminum adjuvants, such as granulomatous abscesses and the increase in regional lymph nodes near the inoculation site. As conclusion, there are no differences between the formulations of B. pertussis with hydroxide or aluminum phosphate resulted in low reactogenicity.

Las vacunas combinadas resultan una estrategia importante en la obtención de vacunas múltiples para la infancia y el uso de adyuvantes es un componente de gran valor en lograr estas combinaciones, además de ser inmunogénicas y protectoras deben tener baja reactogenicidad, cuando se combinan con diferentes antígenos. Por esta razón, se diseñó un estudio de reactogenicidad a dos formulaciones que contenían hidróxido y fosfato de aluminio con antígenos de Bordetella pertussis en ratas Sprague Dawley. Se administró a cada grupo de ensayo una dosis correspondiente de ambas formulaciones en 0,2 mL por vía intramuscular. Se realizaron observaciones clínicas, comportamiento del peso corporal, consumo de agua, alimentos, temperatura corporal, volumen muscular, irritabilidad dérmica y estudios anatomopatológicos macroscópicos, con especial interés en el sitio de inoculación. No se observaron síntomas, ni muertes en los animales durante el estudio. Tampoco se encontraron diferencias entre los grupos experimentales en cuanto al peso corporal, el consumo de agua y de alimentos; los estudios de temperatura corporal y volumetría muscular evidenciaron un ligero incremento en los valores, los cuales involucionaron rápidamente a la normalidad. En el estudio anatomopatológico macroscópico se observaron lesiones a nivel del punto de inoculación, consideradas propias de los adyuvantes que contienen aluminio, tales como formaciones abscedadas de tipo granulomatosas y el aumento de los ganglios linfáticos regionales cercanos al punto de inoculación. Se concluye que las formulaciones en hidróxido y fosfato de aluminio con antígenos de B.pertussis resultaron ser de baja reactogenicidad.

Sonographic features of vaccination granulomas in children with delayed-type hypersensitivity to aluminum.

In this article, we report the sonographic features of vaccination granulomas in three children sensitized to aluminum. Although the recognition of the vaccination granuloma relies on the clinical examination, misdiagnosis is frequent, leading to distressful procedures or prolonged antibiotic administration. In all our cases, sonography revealed a teardrop-shaped echogenic central structure, suggesting the deposition of aluminum crystals along the route of administration with consequent subcutaneous degenerative changes, and a surrounding hypoechoic cap, which reflects the changeable inflammatory reaction and the granuloma formation.

Myalgia and chronic fatigue syndrome following immunization: macrophagic myofasciitis and animal studies support linkage to aluminum adjuvant persistency and diffusion in the immune system.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multifactorial and poorly undersood disabling disease. We present epidemiological, clinical and experimental evidence that ME/CFS constitutes a major type of adverse effect of vaccines, especially those containing poorly degradable particulate aluminum adjuvants. Evidence has emerged very slowly due to the multiplicity, lack of specificity, delayed onset, and frequent medical underestimation of ME/CFS symptoms. It was supported by an epidemiological study comparing vaccinated vs unvaccinated militaries that remained undeployed during Gulf War II. Affected patients suffer from cognitive dysfunction affecting attention, memory and inter-hemispheric connexions, well correlated to brain perfusion defects and associated with a stereotyped and distinctive pattern of cerebral glucose hypometabolism. Deltoid muscle biopsy performed to investigate myalgia typically yields macrophagic myofasciitis (MMF), a histological biomarker assessing longstanding persistency of aluminum agglomerates within innate immune cells at site of previous immunization. MMF is seemingly linked to altered mineral particle detoxification by the xeno/autophagy machinery. Comparing toxicology of different forms of aluminum and different types of exposure is misleading and inadequate and small animal experiments have turned old dogma upside down. Instead of being rapidly solubilized in the extracellular space, injected aluminum particles are quickly captured by immune cells and transported to distant organs and the brain where they elicit an inflammatory response and exert selective low dose long-term neurotoxicity. Clinical observations and experiments in sheep, a large animal like humans, confirmed both systemic diffusion and neurotoxic effects of aluminum adjuvants. Post-immunization ME/CFS represents the core manifestation of "autoimmune/inflammatory syndrome induced by adjuvants" (ASIA).

Alternative to avoid tooth discoloration after regenerative endodontic procedure: a systematic review

Abstract This systematic review aimed to evaluate whether alternative materials to conventional triple antibiotic paste (TAP - metronidazole, ciprofloxacin, and minocycline) and grey mineral trioxide aggregate (GMTA) could avoid tooth discoloration in teeth submitted to Regenerative Endodontic Procedure (REP). It was also investigated if dental bleaching is able to reverse the color of darkened teeth due to REP. The search was conducted in four databases (Medline via PubMed, Scopus, ISI Web of Science and BVS - Virtual health library), following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The retrieved papers were uploaded in the software EndNoteTM and two reviewers independently selected the studies and extracted the data. Only studies in humans (case reports, case series, clinical trials) were included in the review. From 1,122 potentially eligible studies, 83 were selected for full-text analysis, and 38 were included in the review. The included studies were mainly case reports (76.3 %). The studies described a total of 189 teeth submitted to REP. From these, about 54% of teeth presented some degree of discoloration. Most teeth presenting color alteration were treated with TAP, especially when combined with GMTA. Only three studies performed dental bleaching to restore the color of teeth and neither bleaching technique was able to restore the original color of the crowns. The use of alternative materials to TAP and GMTA, such as double antibiotic paste or Ca(OH)2 pastes and white mineral trioxide aggregate or BiodentineTM, reduces the occurrence of tooth discoloration.

Resumo Esta revisão sistemática teve como objetivo avaliar se materiais alternativos à pasta tri-antibiótica convencional (TAP, em Inglês - metronidazol, ciprofloxacina e minociclina) e ao agregado trióxido mineral cinza (MTA cinza) poderiam evitar a descoloração dentária em dentes submetidos ao procedimento endodôntico regenerativo (REP, em Inglês). Também foi investigado se o clareamento dental é capaz de reverter a cor dos dentes escurecidos devido ao REP. A busca foi realizada em quatro bases de dados (Medline via PubMed, Scopus, ISI Web of Science e BVS - Biblioteca Virtual de Saúde), seguindo os Principais Itens para Relatar Revisões Sistemáticas e Meta-análises. Os artigos obtidos foram carregados no software EndNoteTMe dois revisores independentes selecionaram os estudos e extraíram os dados. Apenas estudos em humanos (relatos de casos, séries de casos, ensaios clínicos) foram incluídos na revisão. De 1.122 estudos potencialmente elegíveis, 83 foram selecionados para análise do artigo completo, e 38 foram incluídos na revisão. Os estudos incluídos foram principalmente relatos de casos (76,3%). Os estudos descreveram um total de 189 dentes submetidos ao REP. Destes, cerca de 54% dos dentes apresentaram algum grau de descoloração. A maioria dos dentes com alteração de cor foi tratada com TAP, principalmente quando combinada com MTA-cinza. Apenas três estudos realizaram o clareamento dental para restaurar a cor dos dentes e nem a técnica de clareamento conseguiu restaurar a cor original das coroas. O uso de materiais alternativos à TAP e ao MTA cinza, como a pasta bi-antibiótica, pasta de Ca(OH)2e MTA branco ou BiodentineTM, reduz a ocorrência de descoloração dentária.

Distribution and phytotoxicity of soil labile aluminum fractions and aluminum species in soil water extracts and their effects on tall fescue.

Soil acidification can alter the biogeochemistry of ecosystems and adversely affect biota; however, there are still many debates about the toxicity of aluminum (Al) fractions and Al species in soil:water extracts to plants. In this study, five crude soils with different pH values (4.92-8.51) were collected, seeded with tall fescue and grown in rhizosphere boxes for 120 days. Then, soil properties, labile Al fractions and Al species in soil:water extracts were determined, and their toxicities to plants were analyzed. Our study showed that a stable exchangeable Al fraction (ExAl) pool exists and is supplied by other labile Al fractions. Dissolution of Al from adsorbed hydroxyl-Al fraction (HyAl) and organic-Al fraction (OrAl) may play important roles in soil Al toxicity, as HyAl and OrAl account for major parts of soil labile Al. Additionally, Al3+ and mononuclear hydroxyl-Al species in soil:water extracts have few effects to plants. Nevertheless, high negative correlations were found between Al-F- complexes and tall fescue biomass, indicating their toxicity in the natural soil environment. Thus, in many cases, Al3+ toxicity should not be emphasized because of its lower activity in soil water extracts. Moreover, toxicities of AlF3(aq) and AlF4- to plants should be emphasized, because they have been confirmed in soil water extracts in this study.

Delayed-type hypersensitivity to vaccine aluminum adjuvant causing subcutaneous leg mass and urticaria in a child.

A 3-year-old girl presented with a 7-month history of a waxing and waning left thigh mass associated with pruritus and erythema at the site of two previous DTaP-HepB-IPV vaccinations. Patch testing was positive to aluminum chloride, supporting a diagnosis of vaccine granuloma secondary to aluminum allergy; her symptoms had been well controlled with antihistamines and topical steroids. Injection site granulomas are a benign but potentially bothersome reaction to aluminum-containing immunizations that can be supportively managed, and we encourage strict adherence to the recommended vaccine schedule in this setting. Patch testing is a sensitive, noninvasive diagnostic tool for patients presenting with this clinical finding, and dermatologist awareness can prevent unnecessary medical examination and provide reassurance.

Critical analysis of reference studies on the toxicokinetics of aluminum-based adjuvants.

We reviewed the three toxicokinetic reference studies commonly used to suggest that aluminum (Al)-based adjuvants are innocuous. A single experimental study was carried out using isotopic 26Al (Flarend et al., Vaccine, 1997). This study used aluminum salts resembling those used in vaccines but ignored adjuvant uptake by cells that was not fully documented at the time. It was conducted over a short period of time (28days) and used only two rabbits per adjuvant. At the endpoint, Al elimination in the urine accounted for 6% for Al hydroxide and 22% for Al phosphate, both results being incompatible with rapid elimination of vaccine-derived Al in urine. Two theoretical studies have evaluated the potential risk of vaccine Al in infants, by reference to an oral "minimal risk level" (MRL) extrapolated from animal studies. Keith et al. (Vaccine, 2002) used a high MRL (2mg/kg/d), an erroneous model of 100% immediate absorption of vaccine Al, and did not consider renal and blood-brain barrier immaturity. Mitkus et al. (Vaccine, 2011) only considered solubilized Al, with erroneous calculations of absorption duration. Systemic Al particle diffusion and neuro-inflammatory potential were omitted. The MRL they used was both inappropriate (oral Al vs. injected adjuvant) and still too high (1mg/kg/d) regarding recent animal studies. Both paucity and serious weaknesses of reference studies strongly suggest that novel experimental studies of Al adjuvants toxicokinetics should be performed on the long-term, including both neonatal and adult exposures, to ensure their safety and restore population confidence in Al-containing vaccines.

Feline vaccine-associated sarcomagenesis: Is there an inflammation-independent role for aluminium?

Aluminium has been found in feline vaccine-associated sarcomas. In this study, we investigated the potential for aluminium to contribute directly to tumourigenesis. Our results indicated that an aluminium hydroxide adjuvant preparation was cytotoxic and mutagenic in human-Chinese hamster ovary (CHO) hybrid cells in vitro. Moreover, CHO cells deficient in DNA double strand break (DSB), but not single-strand break (SSB), repair, were particularly sensitive to aluminium exposure compared with repair proficient cells, suggesting that aluminium is associated with DSBs. In contrast to CHO cells, primary feline skin fibroblasts were resistant to the cytotoxic effects of aluminium compounds and exposure to an aluminium chloride salt promoted cell growth and cell cycle progression at concentrations much less than those measured in particular feline rabies vaccines. These findings suggest that aluminium exposure may contribute, theoretically, to both initiation and promotion of tumours in the absence of an inflammatory response.

Safety of available and emerging drug therapies for hyperhidrosis.

INTRODUCTION: Hyperhidrosis affects 4.8% of the U.S. population and has been underestimated by physicians for long time despite considerable interference with quality of life. Many patients suffer from primary (idiopathic) hyperhidrosis which results from over-activity of sympathetic nerves and is restricted to specific body areas, mostly the axillae, palms, soles, or head. Secondary hyperhidrosis is caused by an underlying disease or the intake of medications and often involves large parts of the body. Numerous effective therapies with topical or systemic drugs and surgical options are available. Areas covered: Efficacy and safety data on aluminum salts, anticholinergic drugs for topical or systemic application, and on intradermal botulinum toxin injections used to treat hyperhidrosis are critically evaluated, including data from clinical trials with focus on possible side effects and long-term complications in dispute. Expert opinion: Hyperhidrosis often responds well to available therapies. Depending on the type of hyperhidrosis treatment should be topical/local or systemic. Most of the side effects are mild, transient and easily manageable. In case of systemic treatment with anticholinergics low dosing and up-titration of medication is necessary to avoid severe adverse effects. Concerns about the promotion of breast cancer and Alzheimer disease by topical aluminum salts are unsolved.

Neuroprotective effects of eugenol against aluminiuminduced toxicity in the rat brain.

Aluminium (Al) is a neurotoxic metal that contributes to the progression of several neurodegenerative diseases. The aim of the present study was to evaluate the protective effect of dietary eugenol supplementation against aluminium (Al)- induced cerebral damage in rats. Male Wistar rats were divided into four groups: normal controls, rats fed a diet containing 6,000 µg g-1 eugenol, rats intoxicated daily with aluminium chloride (84 mg kg-1 body weight) p. o. and fed either a basal diet or a eugenol-containing diet. Daily oral administration of Al for four consecutive weeks to rats significantly reduced brain total antioxidant status (TAS) (11.42±0.31 µmol g-1 tissue, p<0.001) with a subsequent significant enhancement of lipid peroxidation (MDA) (32.55±1.68 nmol g-1 tissue, p<0.002). In addition, Al enhanced brain acetylcholinesterase activity (AChE) (46.22±4.90 U mg-1 protein, p<0.001), tumour necrosis factor alpha (TNF-α) (118.72±11.32 pg mg-1 protein, p<0.001), and caspase 3 (Casp-3) (8.77±1.26 ng mg-1 protein, p<0.001) levels, and in contrast significantly suppressed brain-derived neurotrophic factor (BDNF) (82.74±14.53 pg mg-1 protein, p<0.002) and serotonin (5-HT) (1.54±0.12 ng mg-1 tissue, p<0.01) levels. Furthermore, decreased glial fibrillary acidic protein (GFAP) immunostaining was noticed in the striatum of Al-intoxicated rats, compared with untreated controls. On the other hand, co-administration of dietary eugenol with Al intoxication restored brain BDNF (108.76±2.64 pg mg-1 protein) and 5-HT (2.13±0.27 ng mg-1 tissue) to normal levels, enhanced brain TAS (13.43±0.24 µmol g-1 tissue, p<0.05), with a concomitant significant reduction in TNF-α (69.98±4.74 pg mg-1 protein) and Casp-3 (3.80±0.37 ng mg-1 protein) levels (p<0.001), as well as AChE activity (24.50±3.25 U mg-1 protein, p<0.001), and increased striatal GFAP immunoreactivity, compared with Al-treated rats. Histological findings of brain tissues verified biochemical data. In conclusion, eugenol holds potential as a neuroprotective agent through its hydrophobic, antioxidant, and anti-apoptotic properties, as well as its neurotrophic ability against Al-induced brain toxicity in rats.

Breast Cancer and Deodorants/Antiperspirants: a Systematic Review.

BACKGROUND: Over the last decade, the possible association between underarm deodorants/ antiperspirants use and breast cancer risk has raised important interest in the scientific community. The objective of our systematic review is to estimate the pooled risk of deodorants/antiperspirants use for breast cancer. METHODS: All observational studies that evaluated the association between breast cancer risk and deodorants/antiperspirants use were reviewed. We have only identified two case-control studies, carried out between 2002 and 2006. RESULTS: The first study was conducted in USA and investigated the possible relationship between use of products applied for underarm perspiration and the risk for breast cancer in women aged 20-74 years. This population-based case-control study gathered information by in-person interview. The second study was conducted in Iraq and investigated the possible relationship between use of antiperspirants and the risk for breast cancer in women attending a teaching hospital. This study also gathered information by in-person interview. There was no risk of antiperspirants use in the pooled risk (odds ratio 0.40, 95% confidence interval 0.35-0.46). CONCLUSION: Our comprehensive search has identified an insufficient number of studies to conduct a quantitative review and obtain reliable results. Further prospective studies are strongly needed.