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

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

Inflammatory Lung Disease in Rett Syndrome

Rett syndrome (RTT) is a pervasive neurodevelopmental disorder mainly linked to mutations in the gene encoding the methyl-CpG-binding protein 2 (MeCP2). Respiratory dysfunction, historically credited to brainstem immaturity, represents a major challenge in RTT. Our aim was to characterize the relationships between pulmonary gas exchange abnormality (GEA), upper airway obstruction, and redox status in patients with typical RTT (n = 228) and to examine lung histology in a Mecp2-null mouse model of the disease. GEA was detectable in ~80% (184/228) of patients versus ~18% of healthy controls, with “high” (39.8%) and “low” (34.8%) patterns dominating over “mixed” (19.6%) and “simple mismatch” (5.9%) types. Increased plasma levels of non-protein-bound iron (NPBI), F(2)-isoprostanes (F(2)-IsoPs), intraerythrocyte NPBI (IE-NPBI), and reduced and oxidized glutathione (i.e., GSH and GSSG) were evidenced in RTT with consequently decreased GSH/GSSG ratios. Apnea frequency/severity was positively correlated with IE-NPBI, F(2)-IsoPs, and GSSG and negatively with GSH/GSSG ratio. A diffuse inflammatory infiltrate of the terminal bronchioles and alveoli was evidenced in half of the examined Mecp2-mutant mice, well fitting with the radiological findings previously observed in RTT patients. Our findings indicate that GEA is a key feature of RTT and that terminal bronchioles are a likely major target of the disease

Erythrocyte Sedimentation Rate Measurement by VES Matic Cube 80 in Relation to Inflammation Plasma Proteins

Westergren method is considered as the reference procedure to measure Erythrocyte Sedimentation Rate (ESR) by the International Council for Standardization in Haematology. However, a closed automated method, VES Matic Cube 80 (DIESSE S.p.A., Siena, Italy), has been introduced as a new ESR measurement instrument. In this article, we report two different studies: first, we compared the two methods (Westergren and VES Matic Cube 80) and second, we correlated the inflammatory state of 248 patients with their ESR values. Total protein, albumin, C-reactive protein, and other inflammatory proteins were detected in each sample. The results obtained using VES Matic Cube 80 demonstrated a good correlation with those obtained using the Westergren method (Ordinary linear regression: y=0.955x-0.205, r(2) =0.816, P<0.05; Passing-Bablock regression equation: y=0.9153x-0.5763; Bland-Altman analysis: bias 1.2; limits of agreement -17.4-19.9) and with the inflammatory protein levels (CRP: r=0.554 and r=0.498 and Fibrinogen: r=0.699 and r=0.663 for Ves Matic Cube 80 and Westergren, respectively), supporting the hypothesis that VES Matic Cube 80 offers a fast and safe ESR determination, ensuring precision and a very good correlation with the reference method

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

Effects of snake venom proteases on human fibrinogen chains

Proteomic approach is an effective method to study changes in human plasma proteome. Coagulopathies are commonly encountered in victims of viper envenomation which were treated with an administration of immunoglobulin. Unfortunately, this treatment shows significant risk to the patient due to an anaphylactic reaction. Since Echis carinatus Venom (EV) toxins mainly acts both directly and indirectly on fibrinogen, we planned to establish a suitable analysis of its beta (FIBB) e gamma (FIBG) chains. This study will help us to understand the mechanism of envenomation and to find alternative treatments other than the common treatment with the administration of IgG

The belonging of gpMuc, a glycoprotein from Mucuna pruriens seeds, to the Kunitz-type trypsin inhibitor family explains its direct anti-snake venom activity

In Nigeria, Mucuna pruriens seeds are locally prescribed as an oral prophylactic for snake bite and it is claimed that when two seeds are swallowed they protect the individual for a year against snake bites. In order to understand the Mucuna pruriens antisnake properties, the proteins from the acqueous extract of seeds were purified by three chromatographic steps: ConA affinity chromatography, tandem anionic-cationic exchange and gel filtration, obtaining a fraction conventionally called gpMucB. This purified fraction was analysed by SDS-PAGE obtaining 3 bands with apparent masses ranging from 20 to 24 kDa, and by MALDI-TOF which showed two main peaks of 21 and 23 kDa and another small peak of 19 kDa. On the other hand, gel filtration analysis of the native protein indicated a molecular mass of about 70 kDa suggesting that in its native form, gpMucB is most likely an oligomeric multiform protein. Infrared spectroscopy of gpMucB indicated that the protein is particularly thermostable both at neutral and acidic pHs and that it is an all beta protein. All data suggest that gpMucB belongs to the Kunitz-type trypsin inhibitor family explaining the direct anti-snake venom activity of Mucuna pruriens seeds

Proteomic profiling and post-translational modifications in human keratinocytes treated with Mucuna pruriens leaf extract

Mucuna pruriens (Mp) is a plant belonging to the Fabaceae family, with several medicinal properties among which its potential to treat diseases where reactive oxygen species (ROS) play an important role in the pathogeneses. The aim was to investigate the effects of Mp leaf methanolic extract (MPME) on human keratinocytes protein expression and its role in preventing proteins oxidation after oxidative stress (OS) exposure. MATERIAL AND METHODS: The effects of MPME on HaCaT cells protein expression were evaluated treating cells with different concentrations of MPME, with glucose oxidase (GO, source of OS) and with MPME subsequently treated with GO. The protein patterns of treated HaCaT cells are analyzed by two-dimensional gel electrophoresis (2-DE) and compared with that of untreated HaCaT. Immunoblotting was then used to evaluate the role of MPME in preventing the 4-hydroxynonenal protein adducts (4-HNE PAs) formation (marker of OS). RESULTS: Eighteen proteins, identified by mass spectrometry (LC-ESI-CID-MS/MS), were modulated distinctly by MPME in HaCaT. Overall, MPME counteract GO effect, reducing the GO-induced overexpression of several proteins involved in stress response (T-complex protein 1, Protein disulfide-isomerase A3, Protein DJ-1, and Stress-induced-phosphoprotein 1), in cell energy methabolism (Inorganic pyrophosphatase, Triosephosphate isomerase isoform 1, 2-phosphopyruvate-hydratase alpha-enolase, and Fructose-bisphosphate aldolase A isoform 1), in cytoskeletal organization (Cytokeratins 18, 9, 2, Cofilin-1, Annexin A2 and F-actin-capping protein subunit beta isoform 1) and in cell cycle progression (Eukaryotic translation initiation factor 5A-1 isoform B). In addition, MPME decreased the 4-HNE PAs levels, in particular on 2-phosphopyruvate-hydratase alpha-enolase and Cytokeratin 9. CONCLUSIONS: Our findings show that MPME might be helpful in the treatment of OS-related skin diseases by preventing protein post-translational modifications (4-HNE PAs)