Monday, March 17, 2014

Growing evidence that autism is linked to pollution

The journal article is:  Environmental and State-Level Regulatory Factors Affect the Incidence of Autism and Intellectual Disability" .  What they in fact found was a correlation between the rate of congenital malformations of the reproductive system and autism.  They claimed that the rate of congenital malformations of the reproductive system is a surrogate for environmental exposure  to pollution.  That is drawing a long bow indeed.  Pollution may be one cause of malformations but it is not even clear that it is the main cause.  So the data may tell us nothing about pollution.  Crazy

Researchers studied insurance claims from around 100 million people in the U.S., and used congenital malformations in boys as an indicator for parental exposure to environmental toxins.

Several studies have already shown a link between air pollution and autism, but this latest study published in the journal PLOS Computational Biology is one of the largest to put the two together.

'Autism appears to be strongly correlated with rate of congenital malformations of the genitals in males across the country. This gives an indicator of environmental load and the effect is surprisingly strong,' study author Andrey Rzhetsky from the University of Chicago.

The report looked at birth defects associated with parental exposure to pollution and found a 1% increase in the defects corresponded to a 283% increase in autism.

Although the findings are still being analyzed, researchers say they offer support for the theory that environmental pollutants, in addition to genetics, play a role in the development of autism.

Autism is a developmental disorder that interferes with social and communication skills.

It covers a 'spectrum' of conditions that may be mild or very severe, requiring round-the-clock care.

The scientists found a clear link between being pregnant somewhere with high levels of pollution and having an autistic child.

The findings published this week in the PLOS Computational Biology Journal were culled from health records of over 100 million Americans in an effort to shift research from almost exclusively genetic to include environmental factors.

Essentially what happens is during pregnancy there are certain sensitive periods where the fetus is very vulnerable to a range of small molecules – from things like plasticizers, prescription drugs, environmental pesticides and other things,’ said study author Andrey Rzhetsky.

‘Some of these small molecules essentially alter normal development,’ the University of Chicago professor of genetic medicine and human genetics continued. ‘It’s not really well known why, but it’s an experimental observation.’

The defects were especially noticeable in boys’ reproductive systems, Rzhetsky noted.

Women with the highest levels of exposure to these substances were about 50 per cent more likely to have a child who develops autism.

Most pollutants were more strongly associated with autism in boys than in girls.  Boys are in any case much more likely to have the disorder.

Air pollutants contain many toxins that are known to affect neurological function and fetal development.

One in 88 children suffers from autism, and diagnoses in boys greatly outnumber those in girls, according to the Centers for Disease Control and Prevention. No clear cause has been established for the disorder.

‘The environment may play a very significant role in autism, and we should be paying more attention to it,’ said Rzhetsky. ‘We should definitely take into account environmental factors.’


Canine anti-inflammatory points way to 'superbug' killer

Very hopeful

Compounds similar to anti-inflammatory drugs used by veterinarians to treat dogs may be able to fight the drug-resistant "superbugs" that challenge human health, say Australian researchers.

The non-steroidal anti-inflammatory drugs (NSAIDs) act on bacteria in a way that is fundamentally different from current antibiotics and stop bacterial DNA from replicating, says Associate Professor Aaron Oakley of the University of Wollongong, who led the research.

Excitingly today his team reports in Chemistry & Biology that some NSAIDs have a weak antibiotic effect against the notorious drug-resistant "golden staph" infection that is a major problem in post-operative care.

Oakley says the "serendipitous" find highlights the importance of a protein called the 'sliding clamp' as a possible target for a whole new class of antibiotics.

It's a vital protein for all bacteria and, when it is disabled, bacteria are unable replicate or repair their DNA and so can't reproduce, Oakley says.

The clamp acts as a "mobile workstation", tethering molecules that need to interact with the DNA as it replicates.

"The sliding clamp protein is doughnut shaped," he says. "Its job is literally to slide along the DNA. It's elegantly simple - think of a ring on a piece of string."

A special binding site on the sliding clamp can grasp a range of different molecules that need to interact with the 'string' of DNA during replication.

'Holy Grail'

Finding a drug that could interrupt this process was a "Holy Grail" for Oakley who had homed in on a chemical family called carbazoles as possible good blockers of the sliding clamp site.

As part of the drug discovery process, scientists routinely search databases of chemical structures to find structures similar to ones that are already known to give a good effect - in the hope of finding something even better.

A search like this found that carprofen, a non-steroidal anti-inflammatory drug given by vets to dogs, was another member of the carbazole family.

And a literature search showed there had been reports that carprofen had a weak antibiotic effect - but nobody knew how it was acting.

Oakley's team went on to show carprofen did indeed act as a weak antibiotic and using X-ray crystallography they could see the carprofen molecule sits snugly in the binding site of the sliding clamp protein.

He believes it is quite likely that other carbazoles will have stronger antibiotic effects than carprofen, and his team is now investigating these.

Desperate need

Oakley wondered whether other inflammatory drugs such as aspirin also had antibiotic effects.

"We ended up testing about 20 other NSAIDs," he says. "Some didn't work, and some did."

Some of the NSAIDs tested had activity against the infamous golden staph bacteria, Staphylococcus aureus.

"It's a notorious bug," says Oakley, "that has acquired resistance to a lot of different antibiotics and it occurs a lot in post-operative infections. There's a desperate need for new antibiotics due to resistance to the existing compounds."

But the two most commonly used NSAIDs in human medicine - aspirin and ibuprofen - have quite different chemical structures from carprofen and did not show antibiotic activity.

"It's a nice study and it's an important area of research," says Professor Andrew Abell of the University of Adelaide, who was not involved in the work.

"The mechanism of action is totally different to existing antibiotics, so the bugs haven't had a chance to build up resistance to these [compounds].

"I think this highlights that you can't dictate research. This is an observation they made almost in a serendipitous way. You can't plan it. You've got to have your wits about you ... to exploit an observation like this when it comes along."


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