Abstract and Figures

Aluminum is an experimentally demonstrated neurotoxin and the most commonly used vaccine adjuvant. Despite almost 90 years of widespread use of aluminum adjuvants, medical science's understanding about their mechanisms of action is still remarkably poor. There is also a concerning scarcity of data on toxicology and pharmacokinetics of these compounds. In spite of this, the notion that aluminum in vaccines is safe appears to be widely accepted. Experimental research, however, clearly shows that aluminum adjuvants have a potential to induce serious immunological disorders in humans. In particular, aluminum in adjuvant form carries a risk for autoimmunity, long-term brain inflammation and associated neurological complications and may thus have profound and widespread adverse health consequences. In our opinion, the possibility that vaccine benefits may have been overrated and the risk of potential adverse effects underestimated, has not been rigorously evaluated in the medical and scientific community. We hope that the present paper will provide a framework for a much needed and long overdue assessment of this highly contentious medical issue.
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... In the past five decades, growing concerns have been raised among the scientific community and the general public, through sometimes counter-productive conflicts, on the effects and safety of these compounds within the organism. Among these questions, adjuvant kinetics and potential chronic adverse effects, especially when given early in life, are noteworthy [21][22][23][24]. Of note, the epidemiological studies evaluating any links between vaccination and NDDs did not specifically address Al adjuvant exposure, since most of them focused on Al-free vaccines (measles, mumps and rubella, MMR) [25][26][27]. ...
... Vaccination is one of the greatest achievements in medical history, promoting prevention and sometimes the complete eradication of lethal infectious diseases [103,104]. Although traditional vaccines are widely used and tolerated by a vast majority of people, vaccine safety in specific groups of the population has been a matter of concern for the past 50 years, particularly those including ABAs [23,[105][106][107][108]. We cite in the following sections different studies indicating potential problems from a historical point of view. ...
... In particular, the multiple hit model previously described in the present review seems to be adapted to the multiple consecutive immune activations due to the vaccination schedule in the first weeks/months of life [206]. Several studies have thus proposed that ABA exposure may be insidiously harmful for certain children over the short and long term, contributing to the tremendous increase in NDDs, especially ASD, at a young age [23,108,154,163,167,169,208,219,[222][223][224][225] (for a review, see [226]). The main arguments in favor of this hypothesis are the following observations: ...
Article
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Autism spectrum disorder (ASD), schizophrenia, and bipolar disorder are genetically complex and heterogeneous neurodevelopmental disorders (NDDs) resulting from genetic factors and gene-environment (GxE) interactions for which onset occurs in early brain development. Recent progress highlights the link between ASD and (i) immunogenetics, neurodevelopment, and inflammation, and (ii) impairments of autophagy, a crucial neurodevelopmental process involved in synaptic pruning. Among various environmental factors causing risk for ASD, aluminum (Al)containing vaccines injected during critical periods have received special attention and triggered relevant scientific questions. The aim of this review is to discuss the current knowledge on the role of early inflammation, immune and autophagy dysfunction in ASD as well as preclinical studies which question Al adjuvant impacts on brain and immune maturation. We highlight the most recent breakthroughs and the lack of epidemiological, pharmacokinetic and pharmacodynamic data constituting a “scientific gap”. We propose additional research, such as genetic studies that could contribute to identify populations at genetic risk, improving diagnosis, and potentially the development of new therapeutic tools.
... The studies range in subject matter from description of novel autoimmune diseases, through animal studies of aluminium adjuvant toxicity, to studies of the health of vaccinated vs. unvaccinated children. They all seek to prove detrimental effects of vaccines, and their published findings universally support the AVX position: 'observations raise plausible concerns about overall safety of current childhood vaccination programmes' (Tomljenovic and Shaw, 2011a); 'significant correlation exists between the amounts of aluminum (sic) administered…and the current prevalence of autism spectrum disease' (Tomljenovic and Shaw, 2011b); and so on. ...
Thesis
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Vaccine hesitancy, the delay or refusal to vaccinate despite availability, is a current global concern, as it threatens to undermine the effectiveness of a pillar of public health. Lying at one extreme of hesitancy are anti-vaccine activists, or anti-vaxxers. Often, they are organised into groups who avidly campaign against vaccines, aiming to persuade others to withhold from vaccination, despite the overwhelming scientific and medical consensus that it is safe and effective. Campaigns of misinformation and doubt-creation against scientific unanimity have been used to protect commercial interests, for instance of the tobacco and fossil fuel industries. This practice has been termed agnotology, or the cultural production of ignorance. Through a case study of a prominent anti-vaccination organisation, this dissertation shows that these organisations employ the same agnotological tactics to cast doubt on the safety and efficacy of vaccines. The motivation of anti-vaccine organisations to agnotology is considered, before examination of its epistemic consequences, specifically its effects on scientific and public inquiry and understanding of vaccines. One case study indicates that manufactured debate by climate sceptics is epistemically detrimental to climate science by impeding inquiry and progress. Anti-vaccine agnotology does not seem to exert this effect on vaccine science, as new vaccines are developed and introduced. This dissertation argues that the dissent of anti-vaxxers is nonetheless epistemically corrupting and ultimately damaging. It creates a manipulative communication environment in which epistemic vices ‒ character traits which impede effective and responsible inquiry ‒ are encouraged and maintained in anti-vaxxers and the general public.
... De nombreuses controverses ont vues le jour suite à la toxicité possible des adjuvants, de leur élimination et persistance dans l"organisme. C"est le cas de l"aluminium dont le mode d"action est finalement peu connu [229]. Les risques d'auto-immunité, d"inflammation cérébrale à long terme et les complications neurologiques associées sont considérés. ...
Thesis
Le Virus de l'Immunodficience Acquise (HIV)-1 reste un problème majeur de santé publique dans le monde. Malgré des thérapies antivirales efficaces permettant d'allonger la durée de vie des patients infectés par HIV-1, aucun vaccin capable de protéger de l'acquisition du virus ou curer l’infection n'a été homologué. Nous avons développé un vaccin lentiADN innovant, basé sur le squelette du SHIV-KU2, et dépourvu du gène de l'intégrase (CAL-SHIV-IN-). Dans nos études précédentes, nous avons démontré la capacité de ce lentiADN à induire des réponses persistantes composées de cellules précurseurs CD4+ et CD8+ spécifiques de Gag et Nef, de cellules centrales mémoires (Tcm) et de cellules effectrices mémoires (Tem) jusqu'à 80 semaines après l'immunisation chez les macaques cynomolgus. Pour évaluer si ces pools mémoires de cellules peuvent être amplifiés, une cassette contenant le gène IL-7 ou IL-15 a été insérée dans le lentiADN. Les réponses humorales et cellulaires induites par les deux CAL-SHIV-IN- IRES-IL-7 et CAL-SHIV-IN- IRES-IL15 co-injectés ont été comparées à celles induites par le lentiADN parental CAL-SHIV-IN-.Des souris BALB/c et des macaques rhésus ont été immunisés avec les lentiADN plasmidiques, respectivement, et des rappels homologues ont été effectués à 6 et 16 semaines post-immunisation, respectivement.Nos résultats démontrent que la co-administration de CAL-SHIV- IN- IRES-IL-7 et CAL-SHIV-IN- IRES-IL15 entrainaient une production conséquente de cellules T CD4+ et CD8+ spécifiques de Gag et Nef chez les souris et les macaques. Le suivi jusqu'à 40 semaines chez les macaques a mis en évidence leur capacité de réponse à long terme. En outre, la sécrétion de Granzyme B et MIP-1β par les cellules Tcm et Tem spécifiques de Gag ont été amplifiés. De plus, des anticorps plasmatiques IgG non-neutralisants dotés de fonction ADCC ainsi que de fortes réponses IgA mucosales ont été détectés jusqu'à 40 semaines après l'immunisation et renforcés par les adjuvants cytokines chez les macaques.Nous pouvons conclure que la co-expression de l'IL-7 et de l'IL-15 avec les antigènes de notre vaccin lentiADN a entraîné une augmentation de la proportion et de la longévité des cellules T mémoire CD4+ et CD8+ spécifiques au vaccin dans les splénocytes de souris et les PBMC de macaque. En parallèle, il a également provoqué des réponses IgG plasmatiques de longue durée, avec les IgA et IgG mucosaux dans les sécrétions rectales.
... Other alert elements to consider in pharmacovigilance studies must focus on possible rare events such as narcolepsy or others related to the post-vaccination inflammatory syndrome [79]. As shown previously, some of these molecules as aluminum, have a propensity to activate brain microglia and increase the production of inflammatory cytokines, thereby initiating and exacerbating inflammation and excitotoxicity in the brain [80]. Considering that glial cells are highly dynamic and responsive to the diversity of environmental stimuli, microglia, CNS resident macrophage-type immune cells, also can switch from a resting phenotype to a primed state by an initial immune stimulus that is not excessively intense but could facilitate long term neuroinflammation [81]. ...
Article
Coronavirus disease 2019 (COVID-19) represents a global healthcare crisis that has led to morbidity and mortality on an unprecedented scale. While studies on COVID-19 vaccines are ongoing, the knowledge about the reactogenic symptoms that can occur after vaccination and its generator mechanisms can be critical for healthcare professionals to improve compliance with the future vaccination campaign. Because sleep and immunity are bidirectionally linked, sleepiness or sleep disturbance side effects reported after some of the COVID-19 vaccines advise an academic research line in the context of physiological or pathological neuroimmune interactions. On the recognized basis of inflammatory regulation of hypothalamic neurons in sickness behavior, we hypothesized that IL-1β, INF-γ and TNF-α pro-inflammatory cytokines inhibit orexinergic neurons promoting sleepiness after peripheral activation of the innate immune system induced by the novel COVID-19 vaccines. In addition, based on knowledge of previous vaccines and disease manifestations of SARS-CoV-2 infection, it also suggests that narcolepsy must be included as potential adverse events of particular interest to consider in pharmacovigilance studies.
... The inclusion of well-known adjuvants consisting of aluminium-hydroxide or aluminium phosphate particles -which are easily detectable (Gatti and Montanari, 2015), and are known to cause adverse effects (Petrik et al., 2007;Tomljenovic & Shaw, 2011;Butnaru & Shoenfeld, 2015;Gherardi et al., 2019;Crépeaux et al., 2020) -is particularly relevant for children up to the age of five who will typically have already been exposed to multiple doses of vaccines containing such adjuvants. All this, before potentially being exposed to DiCoReTh-injections that are known to have deleterious effects on the immune systems of healthy adult individuals, much less can those injections be regarded as safe for use in children with lower body weight and more limited resources for ridding the body of toxicants through liver, kidney, and lymphatic functions. ...
Article
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The engineered spike protein of SARS-COV-2, and the corresponding infectious disease COVID-19 attributed to it, hold in their grip a large portion of humanity. The global race for a counter strategy quickly turned into a search for a vaccine as the preferred means to contain the virus. An unusually rapid development of different and completely new classes of experimental therapies that would widely be referred to as “vaccines” raised questions about safety, especially with regard to emergency use approval (EUA) being granted with unprecedented urgency and hardly any critical scrutiny. At present, independent researchers, even some former proponents and insiders, of the currently ongoing global experiment represented as a “vaccination” campaign point primarily to the lack of public safety studies based on empirical datasets that should be obtainable for the tens of millions, even hundreds of millions, of doses of mRNA and DNA vector therapeutics being distributed as “vaccines”. Studies regarding efficacy and “side effects” (sometimes fatalities or permanent iatrogenic injuries) of these experimental therapies have been by-passed in favor of short-term field data from real patients which inevitably raises scientific and ethical questions particularly in view of the fact that the persons and entities responsible for public safety hold deep financial and other vested interests in speeding along the distribution of the experimental pharmaceutical products. The lack of an open discussion about the experimental therapies for COVID-19 now being applied across all age groups, even children hardly impacted by COVID-19, is worrying. The core principle of open debate without pre-conceptions or vested interests in outcomes has been and continues to be utterly ignored. We hope to engage scientific discussion that will help decision-makers, the general public, and the media alike to consider the subject-matter of what is at stake in a context of reason rather than panic.
... L'inclusione di noti adiuvanti costituiti da particelle di idrossido di alluminio o fosfato di alluminio, che sono facilmente rilevabili (Gatti e Montanari, 2015) e sono noti per causare effetti avversi (Petrik et al., 2007;Tomljenovic & Shaw, 2011;Butnaru & Shoenfeld, 2015;Gherardi et al., 2019;Crépeaux et al., 2020) -è particolarmente rilevante per i bambini fino all'età di cinque anni che in genere saranno già stati esposti a dosi multiple di vaccini contenenti tali adiuvanti. Tutto questo, prima di essere potenzialmente esposti a iniezioni di TeReCoMa che sono note per avere effetti deleteri sul sistema immunitario di individui adulti sani, tanto meno quelle iniezioni possono essere considerate sicure per l'uso nei bambini con peso corporeo inferiore e risorse più limitate per liberare il corpo da tossicità attraverso il fegato, reni e funzioni linfatiche. ...
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La proteina ingegnerizzata spike della SARS-COV-2 e la corrispondente malattia infettiva COVID-19 attribuita ad essa tengono in pugno una gran parte dell'umanità. La corsa globale per una strategia di contrasto si è rapidamente trasformata nella ricerca di un vaccino come mezzo preferenziale per contenere il virus. Uno sviluppo insolitamente rapido di diverse classi completamente nuove di terapie sperimentali diffuse come "vaccini", ha sollevato interrogativi sulla sicurezza, in particolare per quanto riguarda l'approvazione dell'uso di emergenza (EUA) che è stata concessa con un'urgenza senza precedenti e priva di qualsiasi esame critico contrario. Attualmente, ricercatori indipendenti, come anche alcuni ex proponenti e addetti ai lavori dell'esperimento globale attualmente in corso e rappresentato come una campagna di "vaccinazione", sottolineano soprattutto la mancanza di studi sulla sicurezza della campagna vaccinale che ha finito invece per strutturarsi su set di dati empirici che verranno ottenuti attraverso decine di milioni, anche centinaia di milioni, di dosi di mRNA e terapie vettoriali del DNA distribuite col nome di "vaccini". Gli studi riguardanti l'efficacia e gli "effetti collaterali" (talvolta fatalità o lesioni iatrogene permanenti) di queste terapie sperimentali sono stati omessi a favore di dati a breve termine presi sul campo su pazienti reali. Questa evidenza solleva inevitabilmente questioni scientifiche ed etiche, in particolare in considerazione del fatto che le persone e gli enti responsabili per la sicurezza pubblica hanno vasti interessi finanziari e di altro tipo che li portano ad accelerare la distribuzione di questi prodotti farmaceutici sperimentali. La mancanza di una discussione aperta sulle terapie sperimentali per il COVID-19 ora applicate su tutte le fasce di età, anche i bambini, che difficilmente sono colpiti dal COVID-19, è preoccupante. Il principio fondamentale del dibattito aperto senza preconcetti o sugli interessi nei risultati è stato e continua ad essere completamente ignorato. Speriamo di impegnare una discussione scientifica al fine di aiutare chi deve decidere, l'opinione pubblica e i media a considerare l'oggetto di ciò che è in gioco in un contesto di ragione piuttosto che di panico.
... Despite numerous efforts made in the past, only a handful of adjuvants have been included in licensed human vaccines and few are in clinical trials. Among these vaccine adjuvants, alum (or aluminum salt) is the most widely used, although aluminum is a known neurotoxin and our understanding of its toxicology and pharmacokinetics in the human body is still limited [5,6]. While new types of adjuvants such as those composed of water-in-oil emulsion, squalene, liposomes, other compounds have been developed, they may have higher local reactogenicity and systemic toxicity than alum alone [7,8]. ...
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Background Composed of mineral oil and mycobacteria pathogens, complete Freund’s adjuvant (CFA) is one of the most commonly used adjuvants for antibody production and scientific research due to its high efficiency. However, the dead mycobacteria in CFA can cause many allergic reactions. We propose here a new formulation based on the use of nanodiamonds (NDs) as biocompatible non-allergic additives in incomplete Freund’s adjuvant (IFA) to avoid these adverse effects. Methods Chicken egg ovalbumin (OVA) was used as the antigens and 100-nm NDs after purification by air oxidation and strong oxidative acid washes were used as the additives. Levels of OVA-specific IgG antibody in mouse sera were measured by using enzyme-linked immunosorbent assays (ELISA) after the second and third immunizations of healthy mice with OVA and OVA/ND in IFA or CFA. Abilities of the OVA/ND/IFA vaccination to inhibit the tumor growth of mice inoculated with EL4 cells or OVA-expressing E.G7 cells were examined over 1 month. Results The new formulation worked well as a potent vaccine adjuvant, which could boost the immune responses and reduce the consumption of antigens in producing antibodies of interest in model animals like mice. Additionally, the composites showed distinct therapeutic activities, as proven by the OVA/ND/IFA treatment that effectively inhibited the tumor progression of E.G7-inoculated mice, allowing the animals to survive over 35 days post tumor-cell challenges. About 0.2% of the injected ND particles were found in mouse spleens on day 24 after vaccination of the E.G7-inoculated mice with OVA/ND/IFA. Conclusions The multiple functionality of ND makes it useful as an active and trackable component of a vaccine adjuvant not only to enhance antibody production but also to suppress tumor growth in vivo. The ND-based new formulation can be developed into single-dose vaccines with promising potential for real-world applications.
... However, alum is a relatively weak adjuvant, especially against poorly immunogenic antigens (proteins and peptides), does not induce strong cellular immunity, and is not free from adverse effects, such as macrophagic myofasciitis [141]. To overcome some of these problems, Orr and coworkers developed a lipid-based nanosuspension of synthetic TLR-7/8 ligand, imidazoquinoline (3M-052), which facilitated the adsorption of vaccine antigen (ID93 for tuberculosis and FLSC for HIV) to aluminum oxyhydroxide NPs (<200 nm) [142]. ...
Chapter
Vaccination renders protection against pathogens via stimulation of the body’s natural immune responses. Classical vaccines that utilize whole organisms or proteins have several disadvantages, such as induction of undesired immune responses, poor stability, and manufacturing difficulties. The use of minimal immunogenic pathogen components as vaccine antigens, i.e., peptides, can greatly reduce these shortcomings. However, subunit antigens require a specific delivery system and immune adjuvant to increase their efficacy. Recently, nanotechnology has been extensively utilized to address this issue. Nanotechnology-based formulation of peptide vaccines can boost immunogenicity and efficiently induce cellular and humoral immune responses. This chapter outlines the recent developments and advances of nano-sized delivery platforms for peptide antigens, including nanoparticles composed of polymers, peptides, lipids, and inorganic materials.
Article
Purpose: To report a four-case series of ocular adverse events post an inactivated COVID-19 vaccination in China. Methods: The four patients exhibited ocular inflammatory reactions on the same day after receiving an inactivated SARS-CoV-2 vaccine. Results: All patients underwent detailed ophthalmic examinations, with the medical diagnosis of Vogt-Koyanagi-Harada, Ponser-Schlossman, secondary post-inflammatory glaucoma, and iridocyclitis, respectively. No patients had any other underlying medical conditions causing the ocular complications. The ocular inflammatory reactions of these four patients were resolved with the administration of oral or topical corticosteroids. Conclusion: Our cases remind the ophthalmologist that adverse ocular events may happen after the administration of SARS-CoV-2 vaccine. Since the ocular complications could be resolved with the corticosteroid treatment, the events were considered to be inflammatory reactions caused by the SARS-CoV-2 vaccine.
Article
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Micelles from amphiphilic polylactide-block-poly(N-acryloxysuccinimide-co-N-vinylpyrrolidone) (PLA-b-P(NAS-co-NVP)) block copolymers of 105 nm in size were characterized and evaluated in a vaccine context. The micelles were non-toxic in vitro (both in dendritic cells and HeLa cells). In vitro fluorescence experiments combined with in vivo fluorescence tomography imaging, through micelle loading with the DiR near infrared probe, suggested an efficient uptake of the micelles by the immune cells. The antigenic protein p24 of the HIV-1 was successfully coupled on the micelles using the reactive N-succinimidyl ester groups on the micelle corona, as shown by SDS-PAGE analyses. The antigenicity of the coupled antigen was preserved and even improved, as assessed by the immuno-enzymatic (ELISA) test. Then, the performances of the micelles in immunization were investigated and compared to different p24-coated PLA nanoparticles, as well as Alum and MF59 gold standards, following a standardized HIV-1 immunization protocol in mice. The humoral response intensity (IgG titers) was substantially similar between the PLA micelles and all other adjuvants over an extended time range (one year). More interestingly, this immune response induced by PLA micelles was qualitatively higher than the gold standards and PLA nanoparticles analogs, expressed through an increasing avidity index over time (>60% at day 365). Taken together, these results demonstrate the potential of such small-sized micellar systems for vaccine delivery.
Article
Macrophagic myofasciitis is a condition first reported in 1998, which cause remained obscure until 2001. Over 200 definite cases have been identified in France, and isolated cases have been recorded in other countries. The condition manifests by diffuse myalgias and chronic fatigue, forming a syndrome that meets both Center for Disease Control and Oxford criteria for the so-called chronic fatigue syndrome in about half of patients. One third of patients develop an autoimmune disease, such as multiple sclerosis. Even in the absence of overt autoimmune disease they commonly show subtle signs of chronic immune stimulation, and most of them are of the HLADRB1'01 group, a phenotype at risk to develop polymyalgia rheumatica and rheumatoid arthritis. Macrophagic myofasciitis is characterized by a stereotyped and immunologically active lesion at deltoid muscle biopsy. Electron microscopy, microanalytical studies, experimental procedures, and an epidemiological study recently demonstrated that the lesion is due to persistence for years at site of injection of an aluminum adjuvant used in vaccines against hepatitis 8 virus, hepatitis A virus, and tetanus toxoid. Aluminum hydroxide is known to potently stimulate the immune system and to shift immune responses towards a Th-2 profile. It is plausible that persistent systemic immune activation that fails to switch off represents the pathophysiologic basis of chronic fatigue syndrome associated with macrophagic myofasciitis, similarly to what happens in patients with post-infectious chronic fatigue and possibly idiopathic chronic fatigue syndrome. Therefore, the WHO recommended an epidemiological survey, currently conducted by the French agency AFSSAPS, aimed at substantiating the possible link between the focal macrophagic myofasciitis lesion (or previous immunization with aluminium-containing vaccines) and systemic symptoms. Interestingly, special emphasis has been put on Th-2 biased immune responses as a possible explanation of chronic fatigue and associated manifestations known as the Gulf war syndrome. Results concerning macrophagic myofasciitis may well open new avenues for etiologic investigation of this syndrome. Indeed, both type and structure of symptoms are strikingly similar in Gulf war veterans and patients with macrophagic myofasciitis. Multiple vaccinations performed over a short period of time in the Persian gulf area have been recognized as the main risk factor for Gulf War syndrome. Moreover, the war vaccine against anthrax, which is administered in a 6-shot regimen and seems to be crucially involved, is adjuvanted by aluminium hydroxide and, possibly, squalene, another Th-2 adjuvant. If safety concerns about long-term effects of aluminium hydroxide are confirmed it will become mandatory to propose novel and alternative vaccine adjuvants to rescue vaccine-based strategies and the enormous benefit for public health they provide worlwide.
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Recent evidence indicates that fluoride produces neuronal destruction and synaptic injury by a mechanism that involves free radical production and lipid peroxidation. For a number of pathological disorders of the central nervous system (CNS), excitotoxicity plays a critical role. Various studies have shown that many of the neurotoxic metals, such as mercury, lead, aluminum, and iron also injure neural elements in the CNS by an excitotoxic mechanism. Free radical generation and lipid peroxidation, especially in the face of hypomagnesemia and low neuronal energy production, also magnify excitotoxic sensitivity of neurons and their elements. This paper reviews briefly some of the studies that point to a common mechanism for the CNS neurotoxic effects of fluoride and calls for research directed toward further elucidation of this mechanism.
Article
I. INTRODUCTION During a period of about seven years I have occasionally conducted experiments on the effects of aluminum salts. These studies have convinced me that the use in food of alum or any other aluminum compound is a dangerous practice. That the aluminum ion is very toxic is well known. That"aluminized" food yields soluble aluminum compounds to gastric juice (and stomach contents) has been demonstrated. That such soluble aluminum is in part absorbed and carried to all parts of the body by the blood can no longer be doubted. That the organism can "tolerate" such treatment without suffering harmful consequences has not been shown. It is believed that the facts in this paper will give emphasis to my conviction that aluminum should be excluded from food.1II. EXPERIMENTS BY HOUSE AND GIES ON THE EFFECTS OF ALUMINUM COMPOUNDS ON THE GROWTH OF SEEDLINGS Several years ago, in collaboration
Chapter
Aluminum has been repeatedly implicated in the etiopathology of several human neurodegenerative disorders including Alzheimer's disease. Due largely to the extensive euchromatization of normal brain cell neuronal nuclei and their high intrinsic rate of transcription, one prime target for aluminum appears to be within the nucleic acid compartments of the central nervous system. Generally, the high positive charge density of aluminum (Z2/r = 17.65) acts as a pervasive repressor and demodulator of neural activity. This chapter will review our current knowledge concerning aluminum as a genotoxic 'dementing' cation, particularly as it applies to neural-specific gene transcription and transcription factors in the human brain.
Article
Macrophagic myofasciitis (MMF), a condition newly recognized in France, is manifested by diffuse myalgias and characterized by highly specific myopathological alterations which have recently been shown to represent an unusually persistent local reaction to intramuscular injections of aluminium-containing vaccines. Among 92 MMF patients recognized so far, eight of them, which included the seven patients reported here, had a symptomatic demyelinating CNS disorder. CNS manifestations included hemisensory or sensorimotor symptoms (four out of seven), bilateral pyramidal signs (six out of seven), cerebellar signs (four out of seven), visual loss (two out of seven), cognitive and behavioural disorders (one out of seven) and bladder dysfunction (one out of seven). Brain T2-weighted MRI showed single (two out of seven) or multiple (four out of seven) supratentorial white matter hyperintense signals and corpus callosum atrophy (one out of seven). Evoked potentials were abnormal in four out of six patients and CSF in four out of seven. According to Poser's criteria for multiple sclerosis, the diagnosis was clinically definite (five out of seven) or clinically probable multiple sclerosis (two out of seven). Six out of seven patients had diffuse myalgias. Deltoid muscle biopsy showed stereotypical accumulations of PAS (periodic acid–Schiff)-positive macrophages, sparse CD8+ T cells and minimal myofibre damage. Aluminium-containing vaccines had been administered 3–78 months (median = 33 months) before muscle biopsy (hepatitis B virus: four out of seven, tetanus toxoid: one out of seven, both hepatitis B virus and tetanus toxoid: two out of seven). The association between MMF and multiple sclerosis-like disorders may give new insights into the controversial issues surrounding vaccinations and demyelinating CNS disorders. Deltoid muscle biopsy searching for myopathological alterations of MMF should be performed in multiple sclerosis patients with diffuse myalgias.