The Bordatella pertussis virus is evolving through vaccine-driven adaptation.

PMID: 

Emerg Infect Dis. 2014 Apr ;20(4):626-33. PMID: 24655754

Abstract Title: 

Rapid increase in pertactin-deficient Bordetella pertussis isolates, Australia.

Abstract: 

Acellular vaccines against Bordetella pertussis were introduced in Australia in 1997. By 2000, these vaccines had replaced whole-cell vaccines. During 2008-2012, a large outbreak of pertussis occurred. During this period, 30% (96/320) of B. pertussis isolates did not express the vaccine antigen pertactin (Prn). Multiple mechanisms of Prn inactivation were documented, including IS481 and IS1002 disruptions, a variation within a homopolymeric tract, and deletion of the prn gene. The mechanism of lack of expression of Prn in 16 (17%) isolates could not be determined at the sequence level. These findings suggest that B. pertussis not expressing Prn arose independently multiple times since 2008, rather than by expansion of a single Prn-negative clone. All but 1 isolate had ptxA1, prn2, and ptxP3, the alleles representative of currently circulating strains in Australia. This pattern is consistent with continuing evolution of B. pertussis in response to vaccine selection pressure.

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Artichoke extract improved the expression of genes involved in anti-ageing mechanisms.

PMID: 

Molecules. 2018 Oct 23 ;23(11). Epub 2018 Oct 23. PMID: 30360471

Abstract Title: 

Artichoke Polyphenols Produce Skin Anti-Age Effects by Improving Endothelial Cell Integrity and Functionality.

Abstract: 

Artichoke is a characteristic crop of the Mediterranean area, recognized for its nutritional value and therapeutic properties due to the presence of bioactive components such as polyphenols, inulin, vitamins and minerals. Artichoke is mainly consumed after home and/or industrial processing, and the undersized heads, not suitable for the market, can be used for the recovery of bioactive compounds, such as polyphenols, for cosmetic applications. In this paper, the potential skin anti-age effect of a polyphenolic artichoke extract on endothelial cells was investigated. The methodology used was addressed to evaluate the antioxidant and anti-inflammatory activities and the improvement of gene expression of some youth markers. The results showed that the artichoke extract was constituted by 87% of chlorogenic, 3,5–dicaffeoylquinic, and 1,5–dicaffeoylquinic acids. The extract induced important molecular markers responsible for the microcirculation and vasodilatation of endothelial cells, acted as a potential anti-inflammatory agent, protected the lymphatic vessels from oxidative damage by ROS formation, and enhanced the cellular cohesion by reinforcing the tight junction complex. In addition, the artichoke extract, through the modulation of molecular pathways, improved the expression of genes involved in anti-ageing mechanisms. Finally, clinical testing on human subjects highlighted the enhancement by 19.74% of roughness and 11.45% of elasticity from using an artichoke extract cosmetic formulation compared to placebo cream.

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Varicella vaccine recipients over age 60 shed virus DNA in their saliva up to 4 weeks post-vaccination.

PMID: 

J Infect Dis. 2011 Jun 1 ;203(11):1542-5. PMID: 21592982

Abstract Title: 

Varicella zoster virus DNA at inoculation sites and in saliva after Zostavax immunization.

Abstract: 

Analysis of 36 individuals over age 60 years who were immunized with Zostavax revealed varicella zoster virus (VZV) DNA in swabs of skin inoculation sites obtained immediately after immunization in 18 (50%) of 36 subjects (copy number per nanogram of total DNA, 28 to 2.1× 10(6)) and in saliva collected over 28 days in 21 (58%) of 36 subjects (copy number, 20 to 248). Genotypic analysis of DNA extracted from 9 random saliva samples identified vaccine virus in all instances. In some immunized individuals over age 60, vaccine virus DNA is shed in saliva up to 4 weeks.

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Vaccination can result in demyelination of the central nervous system, with some cases taking up to 5 months to manifest.

PMID: 

Autoimmun Rev. 2014 Mar ;13(3):215-24. PMID: 24514081

Abstract Title: 

The spectrum of post-vaccination inflammatory CNS demyelinating syndromes.

Abstract: 

A wide variety of inflammatory diseases temporally associated with the administration of various vaccines, has been reported in the literature. A PubMed search from 1979 to 2013 revealed seventy one (71) documented cases. The most commonly reported vaccinations that were associated with CNS demyelinating diseases included influenza (21 cases), human papilloma virus (HPV) (9 cases), hepatitis A or B (8 cases), rabies (5 cases), measles (5 cases), rubella (5 cases), yellow fever (3 cases), anthrax (2 cases),meningococcus (2 cases) and tetanus (2 cases). The vast majority of post-vaccination CNS demyelinating syndromes, are related to influenza vaccination and this could be attributed to the high percentage of the population that received the vaccine during the HI1N1 epidemia from 2009 to 2012. Usually the symptoms of the CNS demyelinating syndrome appear few days following the immunization (mean: 14.2 days) but there are cases where the clinical presentation was delayed (more than 3 weeks or even up to 5 months post-vaccination) (approximately a third of all the reported cases). In terms of the clinical presentation and the affected CNS areas, there is a great diversity among the reported cases of post-vaccination acute demyelinating syndromes. Optic neuritis was the prominent clinical presentation in 38 cases, multifocal disseminated demyelination in 30, myelitis in 24 and encephalitis in 17. Interestingly in a rather high proportion of the patients (and especially following influenza and human papiloma virus vaccination-HPV) the dominant localizations of demyelination were the optic nerves and the myelon, presenting as optic neuritis and myelitis (with or without additional manifestations of ADEM), reminiscent to neuromyelitic optica (or, more generally, the NMO-spectrum of diseases). Seven patients suffered an NMO-like disease following HPV and we had two similar cases in our Center. One patient with post-vaccination ADEM, subsequently developed NMO. Overall, the risk of a demyelinating CNS disease following vaccination, although non-negligible, is relatively low. The risk of onset or relapse of CNS demyelination following infections against which the vaccines are aimed to protect, is substantially higher and the benefits of vaccinations surpass the potential risks of CNS inflammation. This does not in any way exempt us from“learning” the lessons taught by the reported cases and searching new and safer ways to improve vaccination techniques and increase their safety profile.

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These findings suggest that Cynara leaves exert antiobesity and antioxidant liver effects in HFD-induced obese rats.

PMID: 

Biomed Res Int. 2019 ;2019:4851279. Epub 2019 May 23. PMID: 31240213

Abstract Title: 

LC-MS/MS Analysis and Hepatoprotective Activity of Artichoke (L.) Leaves Extract against High Fat Diet-Induced Obesity in Rats.

Abstract: 

L. (Artichoke) has been used for the treatment of metabolic disorders. The purpose of the present study was to investigate the hepatoprotective effect ofleaves extract against a high fat diet (HFD) induced rats. This study investigated the most abundant phenolic compounds richleaves extract and it is antihypercholesterolemic and antioxidative effects. The hypercaloric high fat diet (HFD) was treated with 200 mg/kg and 400 mg/kg of ethanol extract (EEA) from leaves ofand atorvastatin (ATOR) (10 mg/kg/day) during an 8-week period. Lipid profile was measured and oxidative stress systematic in hepatic tissue was determined. Our data revealed that HFD-induced hepatic dysfunction manifested by significant abnormal levels of AST, ALT, ALP, LDH, and OCT was accompanied by increasing levels of oxidative stress biomarker (ROS, MDA, and AOPP) while decreasing in antioxidant status. Coadministration of EEA significantly reduced serum lipid profile and hepatic disorders which was confirmed to be histological by reducing the fatty liver deposition in hepatic lobule. These findings suggest thatleaves exert antiobesity and antioxidant liver effects in HFD-induced obese rats.

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Peptide cross-reactivity may potentiate autoimmune cross-reactions.

PMID: 

Front Biosci (Schol Ed). 2012 Jun 1 ;4:1393-401. Epub 2012 Jun 1. PMID: 22652881

Abstract Title: 

Peptide cross-reactivity: the original sin of vaccines.

Abstract: 

Recent numerous studies have demonstrated that an extensive peptide identity platform characterizes entities spanning the entire evolutionary arc from viruses to humans and establishes an immune cross-reactivity potential among viruses and bacteria, as well as between microbial organisms and humans. This peptide commonality presents obstacles to diagnostics, burdens therapeutic vaccinology with harmful collateral effects, and can result in autoimmune diseases. The present study 1) recapitulates the significance of cross-reactivity from the molecular mimicry hypothesis to the phenomenon of microbial immunoevasion; 2) analyzes the implications of cross-reactivity for the self-nonself discrimination issue; 3) highlights the negative role exerted by cross-reactions in translating immunology to effective vaccines; 4) outlines the vicious circle connecting peptide commonality, microbial immune escape, adjuvanted vaccines and autoimmune cross-reactions; and 5) conclusively indicates sequence uniqueness as a basic criterion for designing effective vaccines exempt from autoimmune cross-reactions.

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There is a signficant increased risk of adverse events following immunization in patients with primary immunodeficiency diseases.

PMID: 

Vaccine. 2016 Mar 18 ;34(13):1611-1616. Epub 2016 Feb 2. PMID: 26850760

Abstract Title: 

Adverse events following immunization in patients with primary immunodeficiencies.

Abstract: 

BACKGROUND: Adverse events following immunization (AEFI) requires special consideration in patients with primary immunodeficiency diseases (PID) because they may represent a"red flag"for the initial diagnosis and may cause disease complications. Therefore, the definition of appropriate vaccination schemes is a major issue in PID. The aim of this study is to describe the AEFI in a cohort of PID patients.METHODS: Medical records from 379 PID patients were included. AEFI severity was classified according to the WHO 1999 guidelines. Causality was assessed using the Clinical Immunization Safety Assessment (CISA) 2009 criteria.RESULTS: Evidence of AEFI was found in 26 medical records and represented a total of 29 reactions. Most of the AEFI were observed in patients with idiopathic hypogammaglobulinemia (IHG), chronic granulomatous disease (CGD) and severe combined immunodeficiency (SCID), representing 10, 4 and 4 cases, respectively. A total of 21 reactions were associated with replicative vaccines, 7 of which were serious cases related to Bacille Calmette-Guérin (BCG). BCG was also the vaccine more often associated with definitive AEFI in PID. In addition to BCG-related complications, seizures were the most serious AEFI among PID patients.CONCLUSIONS: Our study included a large cohort of PID patients and confirmed an increased risk of serious AEFI in these populations. The design and implementation of neonatal screening strategies for the early detection of congenital lymphopenias and other PID are urgently needed to avoid serious complications of the BCG vaccine usually applied immediately after birth. Our findings also support the use of the acellular pertussis vaccine to minimize the appearance of seizures in PID patients vaccinated with diphtheria, pertussis and tetanus (DPT).

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Maternal exposure to excess aluminum can lead to neurobehavioral deficits in offspring, according to animal studies.

PMID: 

Neurotoxicol Teratol. 1995 Jul-Aug;17(4):515-21. PMID: 7565498

Abstract Title: 

Reproductive and developmental toxicity of aluminum: a review.

Abstract: 

It is well known that aluminum is a developmental toxicant when administered parenterally. However, until recently, there was little concern about embryo/fetal consequences of aluminum ingestion because bioavailability was considered low. The importance of the route of exposure and the chemical form of the aluminum compound on the developmental toxicity of this element are now well established. Although no evidence of maternal and embryo/fetal toxicity was observed when high doses of aluminum hydroxide were given orally to pregnant rats and mice during organogenesis, signs of maternal and developmental toxicity were found in mice when aluminum hydroxide was given concurrently with citric or lactic acids. On the other hand, studies in rabbits have shown that aluminum-induced behavioral toxicity is greater in adult and aged animals than in young adults. However, maternal dietary exposure to excess A1 during gestation and lactation which did not produce maternal toxicity would be capable of causing permanent neurobehavioral deficits in weanling mice and rats. Adverse effects of parenteral aluminum administration on the mouse male reproductive system have also been reported. The embryo/fetal toxicity of aluminum administration, the potential reproductive toxicology of aluminum exposure, and the neurodevelopmental effects of aluminum are here reviewed.

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Aluminum adjuvants may have potentially distinct roles in vaccine-related adverse events.

PMID: 

Allergy Asthma Clin Immunol. 2018 ;14:80. Epub 2018 Nov 7. PMID: 30455719

Abstract Title: 

Unraveling the enigma: elucidating the relationship between the physicochemical properties of aluminium-based adjuvants and their immunological mechanisms of action.

Abstract: 

Aluminium salts are by far the most commonly used adjuvants in vaccines. There are only two aluminium salts which are used in clinically-approved vaccines, Alhydrogeland AdjuPhos, while the novel aluminium adjuvant used in Gardasilis a sulphated version of the latter. We have investigated the physicochemical properties of these two aluminium adjuvants and specifically in milieus approximating to both vaccine vehicles and the composition of injection sites. Additionally we have used a monocytic cell line to establish the relationship between their physicochemical properties and their internalisation and cytotoxicity. We emphasise that aluminium adjuvants used in clinically approved vaccines are chemically and biologically dissimilar with concomitantly potentially distinct roles in vaccine-related adverse events.

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