measles mumps and rubella vaccination and autism misperception miscommunication vs scientific evidence results of a blinded anonymous italian survey

Herd immunity towards measles, one of the 20 most lethal diseases in human history, has been recently challenged on a global scale. Despite a missing causal relationship, vaccine fear has triggered a global anti vaccine movement. We investigated i) the extent of the vaccination-autism false belief in a selected Italian population from two geographical areas with and without an ongoing epidemics for a potentially vaccination-preventable infectious disease (Neisseria meningitidis, groups C and B); ii) the corresponding information source; and iii) the belief in a possible global conspiracy. Four different population sub-categories (I-general population; II-parents of autistic children; III-paramedics; IV-physicians, biologists and pharmacists; n=424) were administered anonymous questionnaires. A total of 30.1% of the general population and the 54.5% of autism parents participants believed in a vaccine-autism relationship (P<0.0001). The web was the major information source for the general population (35.3%). A total of 41.6% of the general population believes in a cover up of potential conflicts of interests by the Institutions. The belief in the autism-vaccination link was also positively related to the parenthood of an autistic child (OR:5.78, 95%CI: 2.36 to 14.12). We conclude that, against scientific evidence, information source and emotional involvement are major influencers of the misperception in the vaccine-autism paradigm, potentially fuelling the resurgence of vaccinepreventable diseases with major public health consequences

Review Article Isoprostanes and 4-Hydroxy-2-nonenal: Markers or Mediators of Disease? Focus on Rett Syndrome as a Model of Autism Spectrum Disorder

Lipid peroxidation, a process known to induce oxidative damage to key cellular components, has been implicated in several diseases. Following three decades of explorations mainly on in vitro models reproducible in the laboratories, lipid peroxidation has become increasingly relevant for the interpretation of a wide range of pathophysiological mechanisms in the clinical setting. This cumulative effort has led to the identification of several lipid peroxidation end-products meeting the needs of the in vivo evaluation. Among these different molecules, isoprostanes and 4-hydroxy-2-nonenal protein adducts appear to be particularly interesting. This review shows how specific oxidation products, deriving from polyunsaturated fatty acids precursors, are strictly related to the clinical manifestations and the natural history of Rett syndrome, a genetically determined neurodevelopmental pathology, currently classified among the autism spectrum disorders. In our experience, Rett syndrome offers a unique setting for physicians, biologists, and chemists to explore the borders of the lipid mediators concept

Isoprostanoids in clinical and experimental neurological disease models

Isoprostanoids are a large family of compounds derived from non-enzymatic oxidation of polyunsaturated fatty acids (PUFAs). Unlike other oxidative stress biomarkers, they provide unique information on the precursor of the targeted PUFA. Although they were discovered about a quarter of century ago, the knowledge on the role of key isoprostanoids in the pathogenesis of experimental and human disease models remains limited. This is mainly due to the limited availability of highly purified molecules to be used as a reference standard in the identification of biological samples. The accurate knowledge on their biological relevance is the critical step that could be translated from some mere technical/industrial advances into a reliable biological disease marker which is helpful in deciphering the oxidative stress puzzle related to neurological disorders. Recent research indicates the value of isoprostanoids in predicting the clinical presentation and evolution of the neurological diseases. This review focuses on the relevance of isoprostanoids as mediators and potential biomarkers in neurological diseases, a heterogeneous family ranging from rare brain diseases to major health conditions that could have worldwide socioeconomic impact in the health sector. The current challenge is to identify the preferential biochemical pathways that actually follow the oxidative reactions in the neurological diseases and the consequence of the specific isoprostanes in the underlying pathogenic mechanisms

Persistent Unresolved Inflammation in the Mecp2

Rett syndrome (RTT) is a rare neurodevelopmental disorder usually caused by mutations in the X-linked gene methyl-CpG-binding protein 2 (MECP2). Several Mecp2 mutant mouse lines have been developed recapitulating part of the clinical features. In particular, Mecp2-308 female heterozygous mice, bearing a truncating mutation, are a validated model of the disease. While recent data suggest a role for inflammation in RTT, little information on the inflammatory status in murine models of the disease is available. Here, we investigated the inflammatory status by proteomic 2-DE/MALDI-ToF/ToF analyses in symptomatic Mecp2-308 female mice. Ten differentially expressed proteins were evidenced in the Mecp2-308 mutated plasma proteome. In particular, 5 positive acute-phase response (APR) proteins increased (i.e., kininogen-1, alpha-fetoprotein, mannose-binding protein C, alpha-1-antitrypsin, and alpha-2-macroglobulin), and 3 negative APR reactants were decreased (i.e., serotransferrin, albumin, and apolipoprotein A1). CD5 antigen-like and vitamin D-binding protein, two proteins strictly related to inflammation, were also changed. These results indicate for the first time a persistent unresolved inflammation of unknown origin in the Mecp2-308 mouse model

Redox imbalance and morphological changes in skin fibroblasts in typical Rett syndrome.

Evidence of oxidative stress has been reported in the blood of patients with Rett syndrome (RTT), a neurodevelopmental disorder mainly caused by mutations in the gene encoding the Methyl-CpG-binding protein 2. Little is known regarding the redox status in RTT cellular systems and its relationship with the morphological phenotype. In RTT patients (n = 16) we investigated four different oxidative stress markers, F2-Isoprostanes (F2-IsoPs), F4-Neuroprostanes (F4-NeuroPs), nonprotein bound iron (NPBI), and (4-HNE PAs), and glutathione in one of the most accessible cells, that is, skin fibroblasts, and searched for possible changes in cellular/intracellular structure and qualitative modifications of synthesized collagen. Significantly increased F4-NeuroPs (12-folds), F2-IsoPs (7.5-folds) NPBI (2.3-folds), 4-HNE PAs (1.48-folds), and GSSG (1.44-folds) were detected, with significantly decreased GSH (−43.6%) and GSH/GSSG ratio (−3.05 folds). A marked dilation of the rough endoplasmic reticulum cisternae, associated with several cytoplasmic multilamellar bodies, was detectable in RTT fibroblasts. Colocalization of collagen I and collagen III, as well as the percentage of type I collagen as derived by semiquantitative immunofluorescence staining analyses, appears to be significantly reduced in RTT cells. Our findings indicate the presence of a redox imbalance and previously unrecognized morphological skin fibroblast abnormalities in RTT patients

Iron released from an erythrocyte lysate by oxidative stress is diffusible and in redox active form.

AbstractThe incubation of a ghost-free erythrocyte lysate with the oxidizing agent phenylhydrazine resulted in both methemoglobin formation and release of iron in a desferrioxamine (DFO)-chelatable form. The released iron was diffusible, as shown by a dialysis carried out simultaneously with the incubation. When the dialysate was added to erythrocyte ghosts or to microsomes from liver or brain, lipid peroxidation developed in the membranes, indicating that the diffusible iron was in a redox active form. The addition of ATP to the lysate markedly increased both iron diffusion and lipid peroxidation in the membranes subsequently added to the dialysate. The possible implication of these data in some well known pathologies is discussed