Vaccine News – Study – The Blood-Brain Barrier Bottleneck in Brain Drug Development

Study – Systematic review and meta-analysis links autism and toxic metals and highlights the impact of country development status: Higher blood and erythrocyte levels for mercury and lead, and higher hair antimony, cadmium, lead, and mercury.

US National Library of Medicine
National Institutes of Health – 3 Oct 2017

Saghazadeh A – 1, Rezaei N – 2.
Author information
1 Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran; MetaCognition Interest Group (MCIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
2 Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Boston, MA, USA. Electronic address: Rezaei_nima@tums.ac.ir.

Abstract
BACKGROUND:
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder that affects cognitive and higher cognitive functions. Increasing prevalence of ASD and high rates of related comorbidities has caused serious health loss and placed an onerous burden on the supporting families, caregivers, and health care services. Heavy metals are among environmental factors that may contribute to ASD. However, due to inconsistencies across studies, it is still hard to explain the association between ASD and toxic metals. Therefore the objective of this study was to investigate the difference in heavy metal measures between patients with ASD and control subjects.
METHODS:
We included observational studies that measured levels of toxic metals (antimony, arsenic, cadmium, lead, manganese, mercury, nickel, silver, and thallium) in different specimens (whole blood, plasma, serum, red cells, hair and urine) for patients with ASD and for controls. The main electronic medical database (PubMed and Scopus) were searched from inception through October 2016.
RESULTS:
52 studies were eligible to be included in the present systematic review, of which 48 studies were included in the meta-analyses. The hair concentrations of antimony (standardized mean difference (SMD)=0.24; 95% confidence interval (CI): 0.03 to 0.45) and lead (SMD=0.60; 95% confidence interval (CI): 0.17 to 1.03) in ASD patients were significantly higher than those of control subjects. ASD patients had higher erythrocyte levels of lead (SMD=1.55, CI: 0.2 to 2.89) and mercury (SMD=1.56, CI: 0.42 to 2.70). There were significantly higher blood lead levels in ASD patients (SMD=0.43, CI: 0.02 to 0.85). Sensitivity analyses showed that ASD patients in developed but not in developing countries have lower hair concentrations of cadmium (SMD=-0.29, CI: -0.46 to -0.12). Also, such analyses indicated that ASD patients in developing but not in developed lands have higher hair concentrations of lead (SMD=1.58, CI: 0.80 to 2.36) and mercury (SMD=0.77, CI: 0.31 to 1.23). These findings were confirmed by meta-regression analyses indicating that development status of countries significantly influences the overall effect size of mean difference for hair arsenic, cadmium, lead, and mercury between patients with ASD and controls.
CONCLUSION:
The findings help highlighting the role of toxic metals as environmental factors in the etiology of ASD, especially in developing lands. While there are environmental factors other than toxic metals that greatly contribute to the etiology of ASD in developed lands. It would be, thus, expected that classification of ASD includes etiological entities of ASD on the basis of implication of industrial pollutants (developed vs. developing ASD).

Study – Autism: A form of lead and mercury toxicity

Environmental Toxicology and Pharmacology
Volume 38, Issue 3, November 2014, Pages 1016–1024

Highlights
•Autism is a developmental disability characterized by severe, pervasive deficits in social interaction and communications.
•Lead and mercury two of the most common heavy metals in the environment.
•Lead and mercury can lead to autistic disorders.
•Many risk factors contribute to the high level of heavy metals in autistic children.
•Defect in the metabolism of the heavy metals in autistic children also contribute to the high level of these heavy metals in their body.
•Chelating agents can be used in the treatment of the autistic disorders.

Abstract
Aim
Autism is a developmental disability characterized by severe deficits in social interaction and communication. The definite cause of autism is still unknown. The aim of this study is to find out the relation between exposure to Lead and/or mercury as heavy metals and autistic symptoms, dealing with the heavy metals with chelating agents can improve the autististic symptoms.

Method
Blood and hair samples were obtained from 45 children from Upper Egypt with autism between the ages of 2 and 10 years and 45 children served as controls in the same age range, after taken an informed consent and fill a questionnaire to assess the risk factors. The samples were analyzed blindly for lead and mercury by using atomic absorption and ICP-MS. Data from the two groups were compared, then follow up of the autistic children after treatment with chelating agents were done.

Results
The results obtained showed significant difference among the two groups, there was high level of mercury and lead among those kids with autism. Significant decline in the blood level of lead and mercury with the use of DMSA as a chelating agent. In addition, there was decline in the autistic symptoms with the decrease in the lead and mercury level in blood.

Conclusion
Lead and mercury considered as one of the main causes of autism. Environmental exposure as well as defect in heavy metal metabolism is responsible for the high level of heavy metals. Detoxification by chelating agents had great role in improvement of those kids.

Study – The Blood-Brain Barrier: Bottleneck in Brain Drug Development

US National Library of Medicine
National Institutes of Health – Jan 2005

William M. Pardridge
Department of Medicine, UCLA, Los Angeles, California 90024
Address correspondence and reprint requests to William M. Pardridge, M.D., UCLA Warren Hall, 13-164, 900 Veteran Avenue, Los Angeles,

ABSTRACT
Summary: The blood-brain barrier (BBB) is formed by the brain capillary endothelium and excludes from the brain ∼100% of large-molecule neurotherapeutics and more than 98% of all small-molecule drugs. Despite the importance of the BBB to the neurotherapeutics mission, the BBB receives insufficient attention in either academic neuroscience or industry programs. The combination of so little effort in developing solutions to the BBB problem, and the minimal BBB transport of the majority of all potential CNS drugs, leads predictably to the present situation in neurotherapeutics, which is that there are few effective treatments for the majority of CNS disorders. This situation can be reversed by an accelerated effort to develop a knowledge base in the fundamental transport properties of the BBB, and the molecular and cellular biology of the brain capillary endothelium. This provides the platform for CNS drug delivery programs, which should be developed in parallel with traditional CNS drug discovery efforts in the molecular neurosciences.

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Interview recorded on May 5th, 2017 in The United Kingdom

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How to accept Jesus Christ as your personal Saviour

Testimony by Phil Robertson from Duck Dynasty

1 Corinthians 15 Authorized (King James) Version (AKJV)
1 Moreover, brethren, I declare unto you the gospel which I preached unto you, which also ye have received, and wherein ye stand;
2 by which also ye are saved, if ye keep in memory what I preached unto you, unless ye have believed in vain.
3 For I delivered unto you first of all that which I also received, how that Christ died for our sins according to the scriptures;
4 and that he was buried, and that he rose again the third day according to the scriptures:

Hebrews 6 Authorized (King James) Version (AKJV)
1 Therefore leaving the principles of the doctrine of Christ, let us go on unto perfection; not laying again the foundation of repentance from dead works, and of faith toward God,
2 of the doctrine of baptisms, and of laying on of hands, and of resurrection of the dead, and of eternal judgment.
3 And this will we do, if God permit.
4 For it is impossible for those who were once enlightened, and have tasted of the heavenly gift, and were made partakers of the Holy Ghost,
5 and have tasted the good word of God, and the powers of the world to come,
6 if they shall fall away, to renew them again unto repentance; seeing they crucify to themselves the Son of God afresh, and put him to an open shame.
7 For the earth which drinketh in the rain that cometh oft upon it, and bringeth forth herbs meet for them by whom it is dressed, receiveth blessing from God:
8 but that which beareth thorns and briers is rejected, and is nigh unto cursing; whose end is to be burned.

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How to accept Jesus Christ as your personal Saviour

1 Corinthians 15 Authorized (King James) Version (AKJV)
1 Moreover, brethren, I declare unto you the gospel which I preached unto you, which also ye have received, and wherein ye stand;
2 by which also ye are saved, if ye keep in memory what I preached unto you, unless ye have believed in vain.
3 For I delivered unto you first of all that which I also received, how that Christ died for our sins according to the scriptures;
4 and that he was buried, and that he rose again the third day according to the scriptures:

Hebrews 6 Authorized (King James) Version (AKJV)
1 Therefore leaving the principles of the doctrine of Christ, let us go on unto perfection; not laying again the foundation of repentance from dead works, and of faith toward God,
2 of the doctrine of baptisms, and of laying on of hands, and of resurrection of the dead, and of eternal judgment.
3 And this will we do, if God permit.
4 For it is impossible for those who were once enlightened, and have tasted of the heavenly gift, and were made partakers of the Holy Ghost,
5 and have tasted the good word of God, and the powers of the world to come,
6 if they shall fall away, to renew them again unto repentance; seeing they crucify to themselves the Son of God afresh, and put him to an open shame.
7 For the earth which drinketh in the rain that cometh oft upon it, and bringeth forth herbs meet for them by whom it is dressed, receiveth blessing from God:
8 but that which beareth thorns and briers is rejected, and is nigh unto cursing; whose end is to be burned.