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Dive into the research topics where Lucija Tomljenovic is active.

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Featured researches published by Lucija Tomljenovic.


Journal of Alzheimer's Disease | 2011

Aluminum and Alzheimer's Disease: After a Century of Controversy, Is there a Plausible Link?

Lucija Tomljenovic

The brain is a highly compartmentalized organ exceptionally susceptible to accumulation of metabolic errors. Alzheimers disease (AD) is the most prevalent neurodegenerative disease of the elderly and is characterized by regional specificity of neural aberrations associated with higher cognitive functions. Aluminum (Al) is the most abundant neurotoxic metal on earth, widely bioavailable to humans and repeatedly shown to accumulate in AD-susceptible neuronal foci. In spite of this, the role of Al in AD has been heavily disputed based on the following claims: 1) bioavailable Al cannot enter the brain in sufficient amounts to cause damage, 2) excess Al is efficiently excreted from the body, and 3) Al accumulation in neurons is a consequence rather than a cause of neuronal loss. Research, however, reveals that: 1) very small amounts of Al are needed to produce neurotoxicity and this criterion is satisfied through dietary Al intake, 2) Al sequesters different transport mechanisms to actively traverse brain barriers, 3) incremental acquisition of small amounts of Al over a lifetime favors its selective accumulation in brain tissues, and 4) since 1911, experimental evidence has repeatedly demonstrated that chronic Al intoxication reproduces neuropathological hallmarks of AD. Misconceptions about Al bioavailability may have misled scientists regarding the significance of Al in the pathogenesis of AD. The hypothesis that Al significantly contributes to AD is built upon very solid experimental evidence and should not be dismissed. Immediate steps should be taken to lessen human exposure to Al, which may be the single most aggravating and avoidable factor related to AD.


Immunologic Research | 2013

Aluminum in the central nervous system (CNS): toxicity in humans and animals, vaccine adjuvants, and autoimmunity

Christopher A. Shaw; Lucija Tomljenovic

We have examined the neurotoxicity of aluminum in humans and animals under various conditions, following different routes of administration, and provide an overview of the various associated disease states. The literature demonstrates clearly negative impacts of aluminum on the nervous system across the age span. In adults, aluminum exposure can lead to apparently age-related neurological deficits resembling Alzheimer’s and has been linked to this disease and to the Guamanian variant, ALS–PDC. Similar outcomes have been found in animal models. In addition, injection of aluminum adjuvants in an attempt to model Gulf War syndrome and associated neurological deficits leads to an ALS phenotype in young male mice. In young children, a highly significant correlation exists between the number of pediatric aluminum-adjuvanted vaccines administered and the rate of autism spectrum disorders. Many of the features of aluminum-induced neurotoxicity may arise, in part, from autoimmune reactions, as part of the ASIA syndrome.


Journal of Inorganic Biochemistry | 2011

Do aluminum vaccine adjuvants contribute to the rising prevalence of autism

Lucija Tomljenovic; Christopher A. Shaw

Autism spectrum disorders (ASD) are serious multisystem developmental disorders and an urgent global public health concern. Dysfunctional immunity and impaired brain function are core deficits in ASD. Aluminum (Al), the most commonly used vaccine adjuvant, is a demonstrated neurotoxin and a strong immune stimulator. Hence, adjuvant Al has the potential to induce neuroimmune disorders. When assessing adjuvant toxicity in children, two key points ought to be considered: (i) children should not be viewed as small adults as their unique physiology makes them much more vulnerable to toxic insults; and (ii) if exposure to Al from only few vaccines can lead to cognitive impairment and autoimmunity in adults, is it unreasonable to question whether the current pediatric schedules, often containing 18 Al adjuvanted vaccines, are safe for children? By applying Hills criteria for establishing causality between exposure and outcome we investigated whether exposure to Al from vaccines could be contributing to the rise in ASD prevalence in the Western world. Our results show that: (i) children from countries with the highest ASD prevalence appear to have the highest exposure to Al from vaccines; (ii) the increase in exposure to Al adjuvants significantly correlates with the increase in ASD prevalence in the United States observed over the last two decades (Pearson r=0.92, p<0.0001); and (iii) a significant correlation exists between the amounts of Al administered to preschool children and the current prevalence of ASD in seven Western countries, particularly at 3-4 months of age (Pearson r=0.89-0.94, p=0.0018-0.0248). The application of the Hills criteria to these data indicates that the correlation between Al in vaccines and ASD may be causal. Because children represent a fraction of the population most at risk for complications following exposure to Al, a more rigorous evaluation of Al adjuvant safety seems warranted.


Annals of Medicine | 2013

Human papillomavirus (HPV) vaccine policy and evidence-based medicine: Are they at odds?

Lucija Tomljenovic; Christopher A. Shaw

Abstract All drugs are associated with some risks of adverse reactions. Because vaccines represent a special category of drugs, generally given to healthy individuals, uncertain benefits mean that only a small level of risk for adverse reactions is acceptable. Furthermore, medical ethics demand that vaccination should be carried out with the participants full and informed consent. This necessitates an objective disclosure of the known or foreseeable vaccination benefits and risks. The way in which HPV vaccines are often promoted to women indicates that such disclosure is not always given from the basis of the best available knowledge. For example, while the worlds leading medical authorities state that HPV vaccines are an important cervical cancer prevention tool, clinical trials show no evidence that HPV vaccination can protect against cervical cancer. Similarly, contrary to claims that cervical cancer is the second most common cancer in women worldwide, existing data show that this only applies to developing countries. In the Western world cervical cancer is a rare disease with mortality rates that are several times lower than the rate of reported serious adverse reactions (including deaths) from HPV vaccination. Future vaccination policies should adhere more rigorously to evidence-based medicine and ethical guidelines for informed consent.


American Journal of Reproductive Immunology | 2013

Human papilloma virus vaccine and primary ovarian failure: another facet of the autoimmune/inflammatory syndrome induced by adjuvants.

Serena Colafrancesco; Carlo Perricone; Lucija Tomljenovic; Yehuda Shoenfeld

Post‐vaccination autoimmune phenomena are a major facet of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) and different vaccines, including HPV, have been identified as possible causes.


Journal of Inorganic Biochemistry | 2013

Administration of aluminium to neonatal mice in vaccine-relevant amounts is associated with adverse long term neurological outcomes

Christopher A. Shaw; Yongling Li; Lucija Tomljenovic

Our previous ecological studies of autism spectrum disorder (ASD) has demonstrated a correlation between increasing ASD rates and aluminium (Al) adjuvants in common use in paediatric vaccines in several Western countries. The correlation between ASD rate and Al adjuvant amounts appears to be dose-dependent and satisfies 8 of 9 Hill criteria for causality. We have now sought to provide an animal model to explore potential behavioural phenotypes and central nervous system (CNS) alterations using s.c. injections of Al hydroxide in early postnatal CD-1 mice of both sexes. Injections of a high and low Al adjuvant levels were designed to correlate to either the U.S. or Scandinavian paediatric vaccine schedules vs. control saline-injected mice. Both male and female mice in the high Al group showed significant weight gains following treatment up to sacrifice at 6 months of age. Male mice in the high Al group showed significant changes in light-dark box tests and in various measures of behaviour in an open field. Female mice showed significant changes in the light-dark box at both doses, but no significant changes in open field behaviours. These current data implicate Al injected in early postnatal life in some CNS alterations that may be relevant for a better understanding of the aetiology of ASD.


Current Pharmaceutical Design | 2013

Human papillomavirus (HPV) vaccines as an option for preventing cervical malignancies: (how) effective and safe?

Lucija Tomljenovic; Jean Pierre Spinosa; Christopher A. Shaw

We carried out a systematic review of HPV vaccine pre- and post-licensure trials to assess the evidence of their effectiveness and safety. We find that HPV vaccine clinical trials design, and data interpretation of both efficacy and safety outcomes, were largely inadequate. Additionally, we note evidence of selective reporting of results from clinical trials (i.e., exclusion of vaccine efficacy figures related to study subgroups in which efficacy might be lower or even negative from peer-reviewed publications). Given this, the widespread optimism regarding HPV vaccines long-term benefits appears to rest on a number of unproven assumptions (or such which are at odd with factual evidence) and significant misinterpretation of available data. For example, the claim that HPV vaccination will result in approximately 70% reduction of cervical cancers is made despite the fact that the clinical trials data have not demonstrated to date that the vaccines have actually prevented a single case of cervical cancer (let alone cervical cancer death), nor that the current overly optimistic surrogate marker-based extrapolations are justified. Likewise, the notion that HPV vaccines have an impressive safety profile is only supported by highly flawed design of safety trials and is contrary to accumulating evidence from vaccine safety surveillance databases and case reports which continue to link HPV vaccination to serious adverse outcomes (including death and permanent disabilities). We thus conclude that further reduction of cervical cancers might be best achieved by optimizing cervical screening (which carries no such risks) and targeting other factors of the disease rather than by the reliance on vaccines with questionable efficacy and safety profiles.


Journal of Law Medicine & Ethics | 2012

Too Fast or Not Too Fast: The FDA's Approval of Merck's HPV Vaccine Gardasil

Lucija Tomljenovic; Christopher A. Shaw

There are not many public health issues where views are as extremely polarized as those concerning vaccines, and Mercks HPV vaccine Gardasil is a case in point. Ever since gaining the FDAs approval in 2006, Merck has been heavily criticized for their overly aggressive marketing strategies and lobbying campaigns aimed at promoting Gardasil as a mandatory vaccine. Subsequently, questions have been raised as to whether it was appropriate for vaccine manufacturers to partake in public health policies when their conflicts of interests are so obvious. Some of their advertising campaign slogans, such as cervical cancer kills x women per year and your daughter could become one less life affected by cervical cancer, seemed more designed to promote fear rather than evidence-based decision making about the potential benefits of the vaccine. Although, conflicts of interests do not necessarily mean that the product itself is faulty, marketing claims should be carefully examined against factual science data. Currently Gardasil vaccination is strongly recommended by the U.S. and other health authorities while public concerns about safety and efficacy of the vaccine appear to be increasing. This discrepancy leads to some important questions that need to be resolved. The current review examines key issues of this debate in light of currently available research evidence.


Immunologic Research | 2017

Behavioral abnormalities in female mice following administration of aluminum adjuvants and the human papillomavirus (HPV) vaccine Gardasil

Rotem Inbar; Ronen Weiss; Lucija Tomljenovic; Maria Teresa Arango; Yael Deri; Christopher A. Shaw; Joab Chapman; Miri Blank; Yehuda Shoenfeld

Vaccine adjuvants and vaccines may induce autoimmune and inflammatory manifestations in susceptible individuals. To date most human vaccine trials utilize aluminum (Al) adjuvants as placebos despite much evidence showing that Al in vaccine-relevant exposures can be toxic to humans and animals. We sought to evaluate the effects of Al adjuvant and the HPV vaccine Gardasil versus the true placebo on behavioral and inflammatory parameters in female mice. Six-week-old C57BL/6 female mice were injected with either, Gardasil, Gardasilxa0+xa0pertussis toxin (Pt), Al hydroxide, or, vehicle control in amounts equivalent to human exposure. At 7.5xa0months of age, Gardasil and Al-injected mice spent significantly more time floating in the forced swimming test (FST) in comparison with vehicle-injected mice (Al, pxa0=xa00.009; Gardasil, pxa0=xa00.025; Gardasilxa0+xa0Pt, pxa0=xa00.005). The increase in floating time was already highly significant at 4.5xa0months of age for the Gardasil and Gardasilxa0+xa0Pt group (pxa0≤xa00.0001). No significant differences were observed in the number of stairs climbed in the staircase test which measures locomotor activity. These results indicate that differences observed in the FST were unlikely due to locomotor dysfunction, but rather due to depression. Moreover, anti-HPV antibodies from the sera of Gardasil and Gardasilxa0+xa0Pt-injected mice showed cross-reactivity with the mouse brain protein extract. Immunohistochemistry analysis revealed microglial activation in the CA1 area of the hippocampus of Gardasil-injected mice. It appears that Gardasil via its Al adjuvant and HPV antigens has the ability to trigger neuroinflammation and autoimmune reactions, further leading to behavioral changes.


Journal of Toxicology | 2014

Aluminum-induced entropy in biological systems: implications for neurological disease.

Christopher A. Shaw; Stephanie Seneff; Stephen D. Kette; Lucija Tomljenovic; John W. Oller; Robert M. Davidson

Over the last 200 years, mining, smelting, and refining of aluminum (Al) in various forms have increasingly exposed living species to this naturally abundant metal. Because of its prevalence in the earths crust, prior to its recent uses it was regarded as inert and therefore harmless. However, Al is invariably toxic to living systems and has no known beneficial role in any biological systems. Humans are increasingly exposed to Al from food, water, medicinals, vaccines, and cosmetics, as well as from industrial occupational exposure. Al disrupts biological self-ordering, energy transduction, and signaling systems, thus increasing biosemiotic entropy. Beginning with the biophysics of water, disruption progresses through the macromolecules that are crucial to living processes (DNAs, RNAs, proteoglycans, and proteins). It injures cells, circuits, and subsystems and can cause catastrophic failures ending in death. Al forms toxic complexes with other elements, such as fluorine, and interacts negatively with mercury, lead, and glyphosate. Al negatively impacts the central nervous system in all species that have been studied, including humans. Because of the global impacts of Al on water dynamics and biosemiotic systems, CNS disorders in humans are sensitive indicators of the Al toxicants to which we are being exposed.

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Christopher A. Shaw

University of British Columbia

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Dan Li

University of British Columbia

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Yongling Li

University of British Columbia

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