179 Health Research Report 19 APR 2014


HRRPUBLOGO

179  19 APR 2014 /  Compiled by Ralph Turchiano

 

In This Issue:

 

  • Calcium supplementation does not increase coronary heart disease concludes new study
  • Energizing sick mitochondria with vitamin B3
  • Green tea boosts your brain
  • Milk thistle extract silibinin reduces self-renewal of colorectal cancer stem cells
  • Glucosamine promotes longevity by mimicking a low-carb diet
  • Lipid levels during prenatal brain development impact autism: York U study
  • Green is good
  • Forging iron women
  • Tamiflu & Relenza: How effective are they?
  • Low vitamin D linked to fatty liver disease in UK children
  • Chinese herbal remedy as good as methotrexate for treating rheumatoid arthritis
  • Osteoporosis drugs appear to impede cell membrane repair
  • Antibiotics alone are a successful treatment for uncomplicated acute appendicitis in kids
  • Casual marijuana use linked to brain abnormalities in students
  • New meta-analysis builds on the power of whey protein for improved body composition
  • Whooping cough bacterium evolves in Australia
  • Johns Hopkins Bloomberg School of Public Health Researchers Find Association Between SSRI Use During Pregnancy and Autism and Developmental Delays in Boys
  • High disease load reduces mortality of children

 

 Calcium supplementation does not increase coronary heart disease concludes new study

Researchers at Seville congress present result of meta-analysis of randomized controlled trials of calcium supplements with or without vitamin D

The results of a study presented today at the World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases do not support the hypothesis that calcium supplementation, with or without vitamin D, increases coronary heart disease or all-cause mortality risk in elderly women.

The investigators, from centres in Australia, Denmark and the USA, undertook a meta-analysis of randomized controlled trials of calcium supplements with or without vitamin D. They searched for two primary outcomes: coronary heart disease and all-cause mortality verified by clinical review, hospital record or death certificate. The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases were searched from January 1, 1966 – May 24, 2013 for potentially eligible studies, reference lists were checked, and trial investigators were contacted where additional data was required. Eligibility criteria included randomized controlled trials of calcium supplementation with or without vitamin D with events with a mean cohort age >50 years. Trial data were combined using a random-effects meta-analysis to calculate relative risk of heart disease events in participants supplemented with calcium.

Of the 661 potentially eligible reports, 18 met the stringent inclusion criteria, contributing information on 63,564 participants with 3,390 coronary heart disease events and 4,157 deaths from any cause. Five trials contributed coronary heart disease events with pooled relative risk (RR) for calcium of 1.02. And 17 trials contributed to all-cause mortality data with pooled RR for calcium of 0.96. The meta-analysis showed that calcium supplementation with or without vitamin D does not increase coronary heart disease or all-cause mortality risk in elderly women.

Energizing sick mitochondria with vitamin B3

Effective treatment for mitochondrial disease

Vitamins B have recently been turned out to be potent modifiers of energy metabolism, especially the function of mitochondria.

Vitamin B3, (niacin) has been found to delay the signs of aging in animal models.

An international collaboration between the University of Helsinki and École Polytechnique Fédérale de Lausanne reported today in the high-profile journal, Embo Molecular Medicine, that vitamin B3 form, nicotinamide riboside, can slow down the progression of mitochondrial disease, suggesting its potential as a novel therapy approach to adult-onset mitochondrial muscle diseases.

Mitochondria power up all cells in our bodies, by generating fuel, ATP, for all cellular functions. Dysfunction of these cellular engines can cause mitochondrial disorders, which are the most common cause of inherited metabolic diseases in adults and children.

Mitochondrial myopathy is the most frequent form of adult mitochondrial disorder. The typical symptoms in the patients are muscle weakness, pain and cramps. Despite the progressive nature of these diseases, no curative treatment is available.

In their current publication, Dr Nahid Khan in Prof Anu Suomalainen-Wartiovaara’s group showed that feeding mice with food supplemented with B3 form, nicotinamide riboside, delayed their mitochondrial myopathy. The treatment increased mitochondrial mass and function, and cured the structural abnormalities.

These results clearly showed the potential of this vitamin B form, a natural constituent of milk, to activate dysfunctional mitochondrial metabolism, Professor Wartiovaara-Suomalainen states. She continues:

These results are a breakthrough for understanding the mechanisms of human mitochondrial muscle diseases and for exploring the efficient treatment options for these progressive disorders of adults. They also highlight the potent role of niacin in guiding mitochondrial energy metabolism.

Green tea boosts your brain

Green tea is said to have many putative positive effects on health. Now, researchers at the University of Basel are reporting first evidence that green tea extract enhances the cognitive functions, in particular the working memory. The Swiss findings suggest promising clinical implications for the treatment of cognitive impairments in psychiatric disorders such as dementia. The academic journal Psychopharmacology has published their results.

In the past the main ingredients of green tea have been thoroughly studied in cancer research. Recently, scientists have also been inquiring into the beverage’s positive impact on the human brain. Different studies were able to link green tea to beneficial effects on the cognitive performance. However, the neural mechanisms underlying this cognitive enhancing effect of green tea remained unknown.

Better memory

In a new study, the researcher teams of Prof. Christoph Beglinger from the University Hospital of Basel and Prof. Stefan Borgwardt from the Psychiatric University Clinics found that green tea extract increases the brain’s effective connectivity, meaning the causal influence that one brain area exerts over another. This effect on connectivity also led to improvement in actual cognitive performance: Subjects tested significantly better for working memory tasks after the admission of green tea extract.

For the study healthy male volunteers received a soft drink containing several grams of green tea extract before they solved working memory tasks. The scientists then analyzed how this affected the brain activity of the men using magnetic resonance imaging (MRI). The MRI showed increased connectivity between the parietal and the frontal cortex of the brain. These neuronal findings correlated positively with improvement in task performance of the participants. «Our findings suggest that green tea might increase the short-term synaptic plasticity of the brain», says Borgwardt.

Clinical implications

The research results suggest promising clinical implications: Modeling effective connectivity among frontal and parietal brain regions during working memory processing might help to assess the efficacy of green tea for the treatment of cognitive impairments in neuropsychiatric disorders such as dementia.

Milk thistle extract silibinin reduces self-renewal of colorectal cancer stem cells

At the American Association for Cancer Research (AACR) Annual Meeting, a University of Colorado Cancer Center study showed that the chemical silibinin, purified from milk thistle extract, affects cell signaling associated with inflammation and thus also the formation and survival of colorectal cancer stem cells.

 

“We have been deeply involved in this line of research that extends from silibinin to its chemopreventive properties in colorectal cancer, and the current study takes another important step: we see both a likely chemopreventive mechanism and the result of this mechanism in animal models,” says Sushil Kumar, PhD, postdoctoral fellow in the lab of Rajesh Agarwal, PhD, co-program leader of Cancer Prevention and Control at the CU Cancer Center and professor at the Skaggs School of Pharmacy and Pharmaceutical Sciences.

 

The group compared mice chemically treated to develop inflammation-dependent colorectal cancer given silibinin to a control group not given the drug. The results were clear: mice given silibinin showed less incidence of macroadenomas indicative of colorectal cancer, whereas nearly all mice in the control group developed the disease. In addition, in the silibinin group, Kumar and co-authors saw minimal colon inflammation, and minimal incidences of rectal bleeding and rectal prolapse as frequently observed in control mice.

 

“Results indicate that silibinin feeding indeed provided the mice with protective effect,” Kumar says.

 

In addition to demonstrating chemopreventive benefit of silibinin, the current study adds to our understanding of how silibinin offers this benefit. The answer is found in colorectal cancer stem cells (CSCs), which both replicate themselves and also give birth to the cells of colorectal cancers themselves. In the presence of inflammation, CSCs both reproduce themselves (self-renewal) and produce colorectal cancer cells at a greater rate, and cells produced in these conditions are also signaled to survive at greater rates.

 

A key component of this expansion and survival signaling are chemicals called interleukins (IL-4 and-6), which are essential in increasing the number of CSCs and also regulate CSCs survival and function. Silibinin blocks this interleukin 4/6 signaling and so decreases levels of CSC self renewal -promoting mRNAs.

 

“We have been following this CSC signaling back to its source and we see now that silibinin affects the signaling of colorectal cancer stem cells very near their genesis,” Kumar says.

 

It is notoriously difficult to gain approval for clinical trials of chemopreventive agents due to the necessity of treating many, healthy people to affect the very few who would otherwise have developed disease. But Kumar and colleagues hope to further refine the science of silibinin’s chemopreventive properties while eventually exploring this chemical as a strategy for cancer prevention in a human population.

Glucosamine promotes longevity by mimicking a low-carb diet

Life-prolonging effect of a commonly used food supplement in worms and mice

Glucosamine has been freely available in drugstores for many decades. It is widely used to treat arthritis and to prevent joint degeneration. Moreover, glucosamine is known to delay cancer growth. In addition, glucosamine reduces metabolism of nutritive sugars, as was already shown some 50 years ago.

In 2007, Michael Ristow showed that too much nutritive sugar shortens the lifespan of roundworms, a widely studied model organism in ageing research. Conversely, impairing carbohydrate metabolism in these worms was capable of extending lifespan [reference 1]. Unfortunately, the method used in worms at that time unexpectedly appeared to be ineffective in rodents [reference 2], and hence was not studied further.

Extended lifespan by almost 10%

In the recently published study that was performed at ETH Zurich and four German research institutions, Ristow and his colleagues applied glucosamine to roundworms and found that they live around 5% longer than their untreated counterparts.

Next and most importantly, the researchers fed glucosamine to ageing mice in addition to their normal diet. The mice were 100 weeks of age, reflecting a comparative human age of approximately 65 years. A control group of mice received no glucosamine while otherwise receiving an identical diet. Feeding the supplement to mice extended their lifespan by almost 10%, reflecting around 8 additional years of human lifespan. Moreover, glucosamine improved glucose metabolism in elderly mice indicating protection from diabetes, a life-threatening disease most prevalent amongst the elderly.

Mimicking a low-carb diet

Additional analyses revealed that glucosamine feeding promotes the breakdown of amino acids in both worms and mice. Amino acids are key components of proteins, and they become preferentially metabolized in the absence of carbohydrates. As Ristow points out, “this reflects the metabolic state of a low-carb diet due to glucosamine supplementation alone – while these mice ingested the same amount of carbohydrates as their unsupplemented counterparts.” This implies that glucosamine would mimic a low-carb diet in humans as well – without the necessity of reducing the uptake of carbohydrates in our daily diet.

Should we now start taking glucosamine supplements? Ristow replies: “This may be considered a valid option, and yes, I have started taking glucosamine myself.” However, he points out that “diabetics should perform tight blood glucose control, especially during the first weeks.” Interestingly, two recent epidemiological studies on more than 77,000 individuals suggest that intake of glucosamine supplements is associated with reduced mortality in humans [references 3, 4]. “Unlike with our longer living mice, such an association is no definite proof of the effectiveness of glucosamine in humans”, says Ristow. He continues, “But the chances are good, and since unlike with most other potentially lifespan-extending drugs there are no known relevant side effects of glucosamine supplementation, I would tend to recommend this supplement.”

Public Release: 8-Apr-2014

Lipid levels during prenatal brain development impact autism: York U study

– environmental factors such as insufficient dietary supplementations of fatty acids, exposures to infections, various chemicals or drugs can change gene expression and contribute to autism.

– exposure to chemicals in some cosmetics and common over-the-counter medication can affect the levels of these lipids

TORONTO, April 8, 2014 — In a groundbreaking York University study, researchers have found that abnormal levels of lipid molecules in the brain can affect the interaction between two key neural pathways in early prenatal brain development, which can trigger autism. And, environmental causes such as exposure to chemicals in some cosmetics and common over-the-counter medication can affect the levels of these lipids, according to the researchers.

“We have found that the abnormal level of a lipid molecule called Prostaglandin E2 in the brain can affect the function of Wnt proteins. It is important because this can change the course of early embryonic development,” explains Professor Dorota Crawford in the Faculty of Health and a member of the York Autism Alliance Research Group.

This is the first time research shows evidence for cross-talk between PGE2 and Wnt signalling in neuronal stem cells, according to the peer reviewed study published at Cell Communication and Signaling.

Lead researcher and York U doctoral student Christine Wong adds, “Using real-time imaging microscopy, we determined that higher levels of PGE2 can change Wnt-dependent behaviour of neural stem cells by increasing cell migration or proliferation. As a result, this could affect how the brain is organized and wired.  Moreover, we found that an elevated level of PGE2 can increase expression of Wnt-regulated genes — Ctnnb1, Ptgs2, Ccnd1, and Mmp9. “Interestingly, all these genes have been previously implicated in various autism studies.”

Autism is considered to be the primary disorder of brain development with symptoms ranging from mild to severe and including repetitive behaviour, deficits in social interaction, and impaired language. It is four times more prevalent in boys than in girls and the incidence continues to rise. The US Center for Disease Control and Prevention (CDC) data from 2010 estimates that 1 in 68 children now has autism.

“The statistics are alarming. It’s 30 per cent higher than the previous estimate of 1 in 88 children, up from only two years earlier. Perhaps we can no longer attribute this rise in autism incidence to better diagnostic tools or awareness of autism,” notes Crawford. “It’s even more apparent from the recent literature that the environment might have a greater impact on vulnerable genes, particularly in pregnancy. Our study provides some molecular evidence that the environment likely disrupts certain events occurring in early brain development and contributes to autism.”

According to Crawford, genes don’t undergo significant changes in evolution, so even though genetic factors are the main cause, environmental factors such as insufficient dietary supplementations of fatty acids, exposures to infections, various chemicals or drugs can change gene expression and contribute to autism.

York University is helping to shape the global thinkers and thinking that will define tomorrow. York’s unwavering commitment to excellence reflects a rich diversity of perspectives and a strong sense of social responsibility that sets us apart. A York U degree empowers graduates to thrive in the world and achieve their life goals through a rigorous academic foundation balanced by real-world experiential education. As a globally recognized research centre, York is fully engaged in the critical discussions that lead to innovative solutions to the most pressing local and global social challenges. York’s 11 faculties and 27 research centres are thinking bigger, broader and more globally, partnering with 288 leading universities worldwide. York’s community is strong − 55,000 students, 7,000 faculty and staff, and more than 250,000 alumni.

Green is good

 

Natural compound from green tomatoes stimulates muscle growth, improves muscle strength and endurance, and protects against muscle wasting

As unlikely as it sounds, green tomatoes may hold the answer to bigger, stronger muscles.

Using a screening method that previously identified a compound in apple peel as a muscle-boosting agent, a team of University of Iowa scientists has now discovered that tomatidine, a compound from green tomatoes, is even more potent for building muscle and protecting against muscle atrophy.

Muscle atrophy, or wasting, is caused by aging and a variety of illnesses and injuries, including cancer, heart failure, and orthopedic injuries, to name a few. It makes people weak and fatigued, impairs physical activity and quality of life, and predisposes people to falls and fractures. The condition affects more than 50 million Americans annually, including 30 million people over age 60, and often forces people into nursing homes or rehabilitation facilities.

“Muscle atrophy causes many problems for people, their families, and the health care system in general,” says Christopher Adams, M.D., Ph.D., UI associate professor of internal medicine and molecular physiology and biophysics. “However, we lack an effective way to prevent or treat it. Exercise certainly helps, but it’s not enough and not very possible for many people who are ill or injured.”

More muscle, less fat

In a new study, published online April 9 in the Journal of Biological Chemistry, Adams searched for a small molecule compound that might be used to treat muscle atrophy. He zeroed in on tomatidine using a systems biology tool called the Connectivity Map, which was developed at the Broad Institute of MIT and Harvard University. Adams discovered that tomatidine generates changes in gene expression that are essentially opposite to the changes that occur in muscle cells when people are affected by muscle atrophy.

After identifying tomatidine, Adams and his team tested its effects on skeletal muscle. They first discovered that tomatidine stimulates growth of cultured muscle cells from humans.

“That result was important because we are looking for something that can help people,” Adams says.

Their next step was to add tomatidine to the diet of mice. They found that healthy mice supplemented with tomatidine grew bigger muscles, became stronger and could exercise longer. And, most importantly, they found that tomatidine prevented and treated muscle atrophy.

Interestingly, although mice fed tomatidine had larger muscles, their overall body weight did not change due to a corresponding loss of fat, suggesting that the compound may also have potential for treating obesity.

Designing healthier foods

An attractive aspect of tomatidine is that it is a natural compound derived from tomatoes. It is produced when alpha-tomatine, which is found in tomato plants and in green tomatoes in particular, is digested in the gut.

“Green tomatoes are safe to eat in moderation. But we don’t know how many green tomatoes a person would need to eat to get a dose of tomatidine similar to what we gave the mice. We also don’t know if such a dose of tomatidine will be safe for people, or if it will have the same effect in people as it does in mice,” Adams says. “We are working hard to answer these questions, hoping to find relatively simple ways that people can maintain muscle mass and function, or if necessary, regain it.

Adams and his team previously used this same research strategy to discover that ursolic acid, a compound from apple peels, promotes muscle growth.

“Tomatidine is significantly more potent than ursolic acid and appears to have a different mechanism of action. This is a step in the right direction,” Adams says. “We are now very interested in the possibility that several food-based natural compounds such as tomatidine and ursolic acid might someday be combined into science-based supplements, or even simply incorporated into everyday foods to make them healthier.”

 

In an effort to accelerate this research and translate it to people, Adams and his colleagues have founded a biotech company called Emmyon. The company recently received funding from the National Institutes of Health to develop strategies for preserving muscle mass and function during the aging process. The company is also using tomatidine and ursolic acid as natural leads for new medicines targeting muscle atrophy and obesity.

Forging iron women

A new University of Melbourne study has found that women who take iron supplements, experience a marked improvement in their exercise performance.

Published in the Journal of Nutrition, researchers undertook a systematic review and analysis of the effect of iron supplementation to the exercise performance of women in child-bearing years.

Lead researcher, Dr Sant-Rayn Pasricha from the Melbourne School of Population and Global Health found that iron supplementation improved women’s exercise performance, in terms of both the highest level they could achieve at 100% exertion (maximal capacity) and their exercise efficiency at a submaximal exertion. Women who were given iron were able to perform a given exercise using a lower heart rate and at a higher efficiency.

“This was mainly seen in women who had been iron deficient or anaemic at the beginning of the trial and in women who were specifically training, including in elite athletes,” he said.

“The study collected data from many individual smaller studies which generally could not identify this beneficial effect on their own.  However, when we merged the data using meta-analysis, we found this impressive benefit from iron.”

It is the first time researchers have been able to confirm that iron supplementation has beneficial effects on exercise performance.

Dr Pasricha said the findings could have implications for improved performance in athletes and health and general health and well-being in the rest of the population.

“It may be worthwhile screening women, including women training as elite athletes, for iron deficiency, and ensuring they receive appropriate prevention and treatment strategies. Athletes, especially females, are at increased risk of iron deficiency potentially, due to their diets and inflammation caused by excessive exercise,” said Dr Pasricha.

Other studies have shown that women given iron experience improved work productivity.

In addition, this study confirms that iron deficiency can impair exercise performance in women. Iron deficiency can also produce fatigue and lethargy and eventually result in iron deficiency anaemia.

Public Release: 10-Apr-2014

Tamiflu & Relenza: How effective are they?

The BMJ and Cochrane call on government and health policy decision makers to review guidance on use of Tamiflu in light of most recent evidence

Tamiflu (the antiviral drug oseltamivir) shortens symptoms of influenza by half a day, but there is no good evidence to support claims that it reduces admissions to hospital or complications of influenza. This is according to the updated Cochrane evidence review, published today by The Cochrane Collaboration, the independent, global healthcare research network and The BMJ. Evidence from treatment trials confirms increased risk of suffering from nausea and vomiting. And when Tamiflu was used in prevention trials there was an increased risk of headaches, psychiatric disturbances, and renal events. Although when used as a preventative treatment, the drug can reduce the risk of people suffering symptomatic influenza, it is unproven that it can stop people carrying the influenza virus and spreading it to others.

The latest updated Cochrane Review: Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children, is based on full internal reports of 20 Tamiflu (oseltamivir) and 26 Relenza (zanamivir) trials. These trials involved more than 24,000 people and the findings challenge the historical assumption that neuraminidase inhibitors are effective in combating influenza. The evidence also suggests there are insufficient grounds to support the use of Tamiflu in preventing person-to-person spread of influenza. This raises further questions about the most effective way to support drug regulation and public health policy decision-making. Claims about the effectiveness of Tamiflu against complications were a key factor in decisions made by governments around the world to stockpile these drugs in case of a pandemic. The US has spent more than $1.3 billion buying a strategic reserve of antivirals, while in the UK the government has spent almost £424 million for a stockpile of about 40 million doses*.

In 2009, a lack of access to available trial data hampered the efforts of the Cochrane researchers to verify the safety and effectiveness of Tamiflu – and led to questions over decisions to stockpile the drug while the risks and benefits remained uncertain. Today, The BMJ and Cochrane issue a joint call to government and health policy decision makers the world over, asking in light of the latest findings from the Cochrane Review, would you make the same recommendations today, choosing to stockpile Tamiflu?

Compared with a placebo, taking Tamiflu led to a quicker alleviation of influenza-like symptoms of just half a day (from 7 days to 6.3 days) in adults, but the effect in children was more uncertain. There was no evidence of a reduction in hospitalisations or serious influenza complications; confirmed pneumonia, bronchitis, sinusitis or ear infection in either adults or children. Tamiflu also increased the risk of nausea and vomiting in adults by around 4 percent and in children by 5 percent. There was a reported increased risk of psychiatric events of around 1 percent when Tamiflu was used to prevent influenza. Evidence also suggests that Tamiflu prevented some people from producing sufficient numbers of their own antibodies to fight infection.

The worldwide use of Tamiflu, has increased dramatically since the outbreak of H1N1 virus (Swine Flu) in April 2009. It was initially believed that it would reduce hospital admissions and complications of influenza, such as pneumonia, during influenza pandemics. However, the original evidence presented to government agencies around the world was incomplete. The Cochrane Review has benefited from access to more complete reports of the original research, now made available by the manufacturers, Roche and GlaxoSmithKline. Although the review has confirmed small benefits on symptom relief, there is little to justify any belief that it reduces hospital admission or the risk of developing confirmed pneumonia. Along with the evidence of harms from the medication, it raises the question of whether global stockpiling of the drugs is still justifiable given the lack of reliable evidence to support the original claims of its benefits.

Dr David Tovey, Editor-in-Chief, Cochrane, said: “We now have the most robust, comprehensive review on ‘neuraminidase inhibitors’ that exists. Initially thought to reduce hospitalisations and serious complications from influenza, the review highlights that Tamiflu is not proven to do this, and it also seems to lead to harmful effects that were not fully reported in the original publications. This shows the importance of ensuring that trial data are transparent and accessible.”

Dr Tom Jefferson, Dr Carl Heneghan, Dr Peter Doshi, authors of the review, Cochrane Neuraminidase Inhibitors Review Team, said: “Drug approval and use cannot be based on biased or missing information any longer. We risk too much in our population’s health and economy. This updated Cochrane review is the first time a Cochrane systematic review has been based only on clinical study reports and regulator’s comments. It is the first example of open science in medicine using full clinical study reports available without conditions. And therefore the conclusions are that much richer. We urge people not to trust in published trials alone or on comment from conflicted health decision makers, but to view the information for themselves.”

The review clearly recommends that guidance on the use of both neuraminidase inhibitors (oseltamivir and zanamivir) in the prevention or treatment of influenza should be revised to take account of the evidence of small benefit and increased risk of harms.

Dr Fiona Godlee, Editor-in-Chief, The BMJ, said: “This review is the result of many years of struggles to access and use trial data, which was previously unpublished and even hidden from view. It highlights with certainty that future decisions to purchase and use drugs, particularly when on a mass scale, must be based on a complete picture of the evidence, both published and unpublished. We need the full data from clinical trials made available for all drugs in current use. With the new European Clinical Trials Directive bringing in rules for future drugs, it highlights the enormous challenge we face. We need the commitment of organisations and drug companies to make all data available, even if it means going back 20 years. Otherwise we risk another knee-jerk reaction to a potential pandemic. And can we really afford it?”

Low vitamin D linked to fatty liver disease in UK children

London, UK, Saturday 12 April 2014: A UK study[i] investigating the link between low vitamin D status and non-alcoholic fatty liver disease (NAFLD) in British children has identified a genetic variant associated with the disease’s severity.

The research, conducted by the King’s College Hospital Paediatric Liver Centre and the University of Surrey’s School of Biosciences and Medicine, and funded by the Children’s Liver Disease Foundation retrospectively analysed the medical records of 120 paediatric patients with NAFLD.

The findings could carry significant implications for UK clinicians in light of the nation’s rising number of childhood NAFLD cases. High levels of vitamin D deficiency and increasing numbers of rickets cases are thought to be due to the obesity epidemic, more children increasingly choosing to play indoors rather than outside and the excessive use of sun-creams.

EASL’s Educational Councillor Professor Jean-Francois Dufour of the University Clinic for Visceral Surgery and Medicine, University of Bern, Switzerland said: “The data support recent research that revealed an association between low vitamin D status and incidence of NAFLD and is an important development in helping clinicians better understand the growing rate of NAFLD in children throughout the western world.”

“Identifying a gene that impacts or alters the disease is a step in the right direction and could potentially lead to the development of new treatments or diagnostic techniques to address this growing issue,” Professor Dufour continued. “More research into this field is warranted and I look forward to seeing future developments over time.”

NAFLD is the term used to describe fat build-up in liver cells in people who do not drink alcohol excessively.[ii] NAFLD is rapidly becoming the most common liver disease worldwide and is the most common persistent liver disorder in western countries and is estimated to affect up to 10% of Europe’s paediatric population.[iii] The disease has an estimated overall prevalence of 20% to 30% across Europe.[iv],[v]

Patients were found to have low vitamin D blood levels throughout the entire year, not just in the winter months, plus the majority of samples were found to be deficient or insufficient in vitamin D status compared to national UK and US health standards. The study also detected a variant of the NADSYN1 gene which was associated with NAFLD severity in patients.

Chinese herbal remedy as good as methotrexate for treating rheumatoid arthritis

And combination of Tripterygium wilfordii Hook F plus methotrexate even better

A traditional Chinese herbal remedy used to relieve joint pain and inflammation works as well as methotrexate, a standard drug treatment that is frequently prescribed to control the symptoms of active rheumatoid arthritis, reveals research published online in the Annals of the Rheumatic Diseases.

Furthermore, combining the herbal remedy with methotrexate—the disease modifying drug (DMARD) most commonly used to treat rheumatoid arthritis—was more effective than treatment with methotrexate alone, the findings showed.

Triptergium wilfordii Hook F, or TwHF for short, is used in traditional Chinese medicine to treat joint pain, swelling, and inflammation, and is already approved for the treatment of rheumatoid arthritis in China.

The research team randomly assigned 207 patients with active rheumatoid arthritis to one of three treatment groups: methotrexate 12.5 mg once a week; or TwHF 20 mg three times a day; or a combination of the two over a period of 24 weeks.

The researchers wanted to find out which of these approaches would sufficiently alleviate symptoms to reach an ACR 50 response.

This indicates a 50% improvement in the number of tender or swollen joints and other criteria including pain, disability, and the doctor’s assessment of disease severity. It’s a measure defined by the American College of Rheumatology.

Most (174; 84%) of the participants completed the full 24 weeks of the trial. The proportion of patients achieving ACR 50 was almost 46.5% in those treated with methotrexate alone; 55% in those treated with TwHF alone; and just under 77% in those treated with both.

Similar clinically significant patterns of improvement in disease activity and remission rates also occurred among the three treatment groups.

There was little difference between the frequency or type of side effects experienced in the different treatment groups, although the number of women who developed irregular periods was slightly higher in those treated with TwHF.

More than 300 compounds have been identified in TwHF, including diterpenoids, which experimental research suggests can suppress genes controlling inflammation and dampen down the immune response, the authors point out.

And an extract of the root has recently been investigated for its potential to treat automimmune diseases and some cancers, say the researchers.

They caution that 24 weeks is too short a time to evaluate disease progression, and that the dose of methotrexate used in the trial is lower than that typically given to patients in the West.

But they suggest that TwHF could be a promising approach to the treatment of active rheumatoid arthritis, particularly as not all patients respond to DMARDs, and because these drugs are expensive.

###

[Comparison of Tripterygium wilfordii Hook F with methotrexate in the treatment of active rheumatoid arthritis (TRIFRA): a randomised, controlled clinical trial Online First doi 10.1136/annrheumdis-2013-204807]

Osteoporosis drugs appear to impede cell membrane repair

AUGUSTA, Ga. –A class of drugs widely used to treat osteoporosis appears to impede a cell’s ability to repair a protective outer membrane that helps determine what enters and exits, researchers report.

The inability to quickly repair a membrane is lethal to a cell and may help explain the rare and serious side effect of jawbone destruction that can occur following dental work in patients taking these drugs, said Caroline Lewis, a sophomore at the Medical College of Georgia at Georgia Regents University.

“The bottom line is it inhibits cell membrane repair in two distinct cell types,” Lewis said. She is among five winners of the 2014 National Medical Students Competition of the American College of Physicians. Lewis presented her work April 12 during the college’s Internal Medicine 2014 meeting in Orlando.

Working in the lab of Dr. Paul McNeil, an MCG cell biologist specializing in cell membrane repair, Lewis found that kidney epithelial cells from monkeys and muscle cells from mice both lost their ability to quickly repair their outer membrane after exposure to zoledronate, a commonly used bisphosphonate, Lewis said. Without drug exposure, cells quickly recovered from a microscope laser injury.

“That is healthy, normal repair,” she said, citing a video showing the normal cell experiencing only a brief flicker of fluorescence where hit by a laser. On the other hand, zoledronate-exposed cells quickly filled with a fluorescent dye the researchers placed in the petry dish.

“All this dye coming into the cell means there is still a disruption and no repair occurred to sort of mend the fence,” Lewis said. “We know these cells are dying, Basically these videos speak for themselves.”

“It’s a paradox,” added McNeil. “On the one hand, (the drug) is given to people mainly to promote bone health, increase bone density. But in the case of a jaw that has suffered, for example, a tooth extraction, the exact opposite occurs.”

He theorized cell membrane repair was contributing to destruction of the jawbone and the lining of the mouth after a 2012 report in the Journal of Proteome Research that bisphosphonates bind to cell membrane proteins vital to membrane repair. Since the severe side effect seems to occur only following dental work, McNeil made the connection.

While it’s not clear whether this failure to repair is happening in other parts of the body, McNeil and Lewis note that cell membrane repair is typically a constant throughout the body.

“Pretty much every day of our life, even exercising, you are contracting your muscles, the muscle cells rub past each other and that friction causes microscopic tears in the membrane,” Lewis said. “If those cells can’t repair an injury, they die because they can’ t maintain internal homeostasis.”

Next steps include more cell studies, including those on jawbone cells, McNeil said. Kidney epithelial cells and muscle cells used in this study are routinely used in cell membrane repair research, and cell repair mechanisms tend to be consistent across cell types, even across different species, McNeil noted.

He also is pursuing the potential protective properties of vitamin E for these patients. McNeil reported in December 2011 in the journal Nature Communications that vitamin E, a powerful antioxidant found in most foods, helps repair tears in the plasma membrane. In the meantime, Lewis suggests that patients taking the drugs talk with their physicians if they have concerns. Some physicians and dentists recommend a drug holiday for these patients before having dental work.

Bisphosphonates are thought to work primarily by inhibiting bone-consuming cells called osteoclasts, which balance the activty of bone-producing osteoblasts, a balance that’s lost in osteoporosis. Bisphosophonate-related osteonecrosis of the jaw, or BRON, is among a fairly long list of side effects for these drugs, including rashes swelling, upper chest pain, irregular heartbeat, and painful or swollen gums and loosening of the teeth, according to MedlinePlus Drug Information.

Bisphosphonates also are used to treat hypercalcemia, high blood levels of calcium that can result from cancer, an overactive parathyroid, and calcium supplements; as well as multiple myeloma, cancer of the plasma cells; and cancer that has spread to the bone. Lewis, who is from Savannah, Ga., worked with McNeil last summer as a participant in the MCG Dean’s Student Summer Research Program.

Antibiotics alone are a successful treatment for uncomplicated acute appendicitis in kids

Using antibiotics alone to treat children with uncomplicated acute appendicitis is a reasonable alternative to surgery that leads to less pain and fewer missed school days, according to a pilot study. The research, led by a team at Nationwide Children’s Hospital and published online April 12 in the Journal of the American College of Surgeons, is the first prospective study on nonoperative management of acute appendicitis in pediatric patients in the United States.

Researchers enrolled 77 patients age 7 to 17 who were diagnosed with uncomplicated acute appendicitis by a surgeon in the Emergency Department at Nationwide Children’s between October 2012 and October 2013. Participants had experienced abdominal pain for no more than 48 hours; had a white blood cell count below 18,000; underwent an ultrasound or CT scan to rule out rupture and to verify that their appendix was 1.1 cm thick or smaller; and had no evidence of abscess or fecalith, which is hard stone made of calcified stool.

Thirty patient families chose antibiotics alone and 47 opted for surgery. Those in the non-operative group were admitted to the hospital and received IV antibiotics for at least 24 hours, followed by oral antibiotics for a total of 10 days after discharge. Among those patients, 93 percent showed improvement within 24 hours. Three patients ultimately underwent an appendectomy when the symptoms failed to resolve, but none experienced an appendix rupture.

“Based on the current study, children with uncomplicated appendicitis are good candidates for non-operative management,” says Katherine J. Deans, MD, who led the study with Peter C. Minneci, MD. The pair are co-directors of the Center for Surgical Outcomes and principal investigators in the Center for Innovation in Pediatric Practice in The Research Institute at Nationwide Children’s.

Appendicitis, caused by a bacterial infection in the appendix, is the most common reason for emergency abdominal surgery in children, sending more than 80,000 young people to the operating room each year. Although many of these cases are severe and require surgery, there are a good number that would be candidates for treatment with antibiotics alone, Dr. Minneci says.

“About 20 percent of the kids with appendicitis who came here had uncomplicated appendicitis, which is would what I would expect to see at any major children’s hospital,” he says, adding that the results from their study are similar to those from a series of European studies performed in adults that have found that in most cases, appendicitis doesn’t require surgery at all.

To study the option further, Drs. Deans and Minneci are coordinating efforts by 10 other pediatric hospitals in the Midwest Pediatric Surgical Consortium to enroll as many 800 children over the next few years in similar trials.

“With our pilot project, we started with the group of patients who would be most likely to have success with an antibiotics-only approach and would be least likely to be harmed, but the next step is to try to slowly add some of the patients who were excluded in the preliminary study to see how well they do,” Dr. Minneci says. “It may get to the point that nonoperative management becomes the initial therapy for all appendicitis, but we won’t know that until we do further studies.”

As with the pilot project, future studies will follow a patient-choice model, meaning participants will not be randomized to one treatment group or the other.

“Patients are more likely to participate in research if they are able to make a choice and not be randomized to one of the two treatment options,” Dr. Minneci says. “That is something that’s different about this trial.”

The notion of involving parents and patients in the decision-making process is under study in a related project led by Drs. Deans and Minneci. Funded by a $1.6 million grant from the Patient-Centered Outcomes Research Institute (PCORI), the researchers are studying the impact of using a novel computer application that engages patients and families as critical decision makers in choosing the therapy that is best for them. The interactive tool offers information about the causes of appendicitis, treatment options and what to expect during and after each kind of treatment. In this study, some participants will receive an iPad with the app to complement their discussions with a surgeon and the others will only talk with the surgeons.

“Through the pilot study, we have learned about the important questions, concerns and values the families have with regard to both operative and nonoperative management of acute appendicitis,” Dr. Deans says. “Understanding those concerns prompted us to do the PCORI study, which is really about improving shared decision making with parents and families.”

Casual marijuana use linked to brain abnormalities in students

First study to show dramatic effects of small time use; more ‘joints’ equal more damage

CHICAGO — Young adults who used marijuana only recreationally showed significant abnormalities in two key brain regions that are important in emotion and motivation, scientists report. The study was a collaboration between Northwestern Medicine® and Massachusetts General Hospital/Harvard Medical School.

This is the first study to show casual use of marijuana is related to major brain changes. It showed the degree of brain abnormalities in these regions is directly related to the number of joints a person smoked per week. The more joints a person smoked, the more abnormal the shape, volume and density of the brain regions.

“This study raises a strong challenge to the idea that casual marijuana use isn’t associated with bad consequences,” said corresponding and co-senior study author Hans Breiter, M.D. He is a professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine and a psychiatrist at Northwestern Memorial Hospital.

“Some of these people only used marijuana to get high once or twice a week,” Breiter said. “People think a little recreational use shouldn’t cause a problem, if someone is doing OK with work or school. Our data directly says this is not the case.”

The study will be published April 16 in the Journal of Neuroscience.

Scientists examined the nucleus accumbens and the amygdala — key regions for emotion and motivation, and associated with addiction — in the brains of casual marijuana users and non-users. Researchers analyzed three measures: volume, shape and density of grey matter (i.e., where most cells are located in brain tissue) to obtain a comprehensive view of how each region was affected.

Both these regions in recreational pot users were abnormally altered for at least two of these structural measures. The degree of those alterations was directly related to how much marijuana the subjects used.

Of particular note, the nucleus acccumbens was abnormally large, and its alteration in size, shape and density was directly related to how many joints an individual smoked.

“One unique strength of this study is that we looked at the nucleus accumbens in three different ways to get a detailed and consistent picture of the problem,” said lead author Jodi Gilman, a researcher in the Massachusetts General Center for Addiction Medicine and an instructor in psychology at Harvard Medical School. “It allows a more nuanced picture of the results.”

Examining the three different measures also was important because no single measure is the gold standard. Some abnormalities may be more detectable using one type of neuroimaging analysis method than another. Breiter said the three measures provide a multidimensional view when integrated together for evaluating the effects of marijuana on the brain.

“These are core, fundamental structures of the brain,” said co-senior study author Anne Blood, director of the Mood and Motor Control Laboratory at Massachusetts General and assistant professor of psychiatry at Harvard Medical School. “They form the basis for how you assess positive and negative features about things in the environment and make decisions about them.”

Through different methods of neuroimaging, scientists examined the brains of young adults, ages 18 to 25, from Boston-area colleges; 20 who smoked marijuana and 20 who didn’t. Each group had nine males and 11 females. The users underwent a psychiatric interview to confirm they were not dependent on marijuana. They did not meet criteria for abuse of any other illegal drugs during their lifetime.

The changes in brain structures indicate the marijuana users’ brains are adapting to low-level exposure to marijuana, the scientists said.

The study results fit with animal studies that show when rats are given tetrahydrocannabinol (THC) their brains rewire and form many new connections. THC is the mind-altering ingredient found in marijuana.

“It may be that we’re seeing a type of drug learning in the brain,” Gilman said. “We think when people are in the process of becoming addicted, their brains form these new connections.”

In animals, these new connections indicate the brain is adapting to the unnatural level of reward and stimulation from marijuana. These connections make other natural rewards less satisfying.

“Drugs of abuse can cause more dopamine release than natural rewards like food, sex and social interaction,” Gilman said. “In those you also get a burst of dopamine but not as much as in many drugs of abuse. That is why drugs take on so much salience, and everything else loses its importance.”

The brain changes suggest that structural changes to the brain are an important early result of casual drug use, Breiter said. “Further work, including longitudinal studies, is needed to determine if these findings can be linked to animal studies showing marijuana can be a gateway drug for stronger substances,” he noted.

Because the study was retrospective, researchers did not know the THC content of the marijuana, which can range from 5 to 9 percent or even higher in the currently available drug. The THC content is much higher today than the marijuana during the 1960s and 1970s, which was often about 1 to 3 percent, Gilman said.

Marijuana is the most commonly used illicit drug in the U.S. with an estimated 15.2 million users, the study reports, based on the National Survey on Drug Use and Health in 2008. The drug’s use is increasing among adolescents and young adults, partially due to society’s changing beliefs about cannabis use and its legal status.

A recent Northwestern study showed chronic use of marijuana was linked to brain abnormalities. “With the findings of these two papers,” Breiter said, “I’ve developed a severe worry about whether we should be allowing anybody under age 30 to use pot unless they have a terminal illness and need it for pain.”

.

New meta-analysis builds on the power of whey protein for improved body composition

Whey protein consumption may lead to significant decreases in body weight and body fat and significant increases in lean body mass

Rosemont, IL (April 15, 2014) – New researchi published in the March/April 2014 issue of the Journal of the American College of Nutrition shows whey protein, either as a supplement combined with resistance exercise or as part of a weight-loss or weight-maintenance diet, may provide men and women benefits related to body composition.

The meta-analysis included 14 randomized controlled trials with a total of 626 adult participants. When researchers analyzed those weight loss studies that used whey protein to replace calories in the diet, participants had a decrease in body weight of 4.2 kg (9.2 pounds), on average, compared to baseline values with whey protein intake. Additionally, after analyzing muscle protein synthesis studies that included resistance exercise along with whey provisions, researchers found that participants had a statistically significant increase in lean body mass of 2.24 kg (4.9 pounds,) on average, when whey protein was used in conjunction with resistance exercise.

“There is a growing body of research that supports the benefits of whey protein for weight maintenance and lean body mass,” said Dominik D. Alexander, PhD, MSPHii, principal investigator. “By conducting this meta-analysis we were able to better evaluate the collective power of each individual study. The results indicate that there is something unique about whey protein, compared to other protein sources and carbohydrates, when it comes to building lean body mass and maintaining or losing weight.”

Whey protein is a high-quality protein naturally found in dairy. It is a complete protein containing all of the essential amino acids (“building blocks”) the body needs, and is rapidly digestible. Whey protein is also one of the best sources of a subgroup of three essential amino acids, called branched-chain amino acids (BCAAs), which include leucine, isoleucine and valine. Unlike other amino acids, BCAAs are almost exclusively taken up and used by muscle. And, among common food sources of BCAAs, whey protein contains one of the highest levels of leucine, which has been shown to influence muscle growth.

This research is one of several studies supported by the Whey Protein Research Consortium, an international partnership of dairy cooperatives, associations, processors and multinational companies working together to support whey research. The Consortium’s first studyiii by Dr. David Baer, USDA, found that daily consumption of whey protein, but not soy protein, led to lower body weight, body fat and waist circumference compared to carbohydrates in free-living overweight and obese adults.

“These research findings support the Consortium’s goal to create a strong scientific foundation demonstrating the health and wellness benefits of whey protein,” said Bryan Helwig, PhD, Whey Protein Research Consortium. “This research provides further evidence demonstrating the benefits of whey proteins as they relate to body composition,” said Dr. Helwig.

The meta-analysis can be accessed here: http://www.tandfonline.com/doi/full/10.1080/07315724.2013.875365#.U0wBPMf6Ges

Study Details

The Study: A meta-analysis was conducted to examine the effect of whey protein (WP),with or without resistance exercise, on body weight and body composition in randomized controlled trials (RCTs) conducted in generally healthy adult study populations. A comprehensive literature search was conducted to identify RCTs that investigated WP (concentrate, isolate, or hydrolystate) and body weight, body mass index (BMI), body fat,lean body mass (LBM), fat-free mass (FFM), and waist circumference. Random effects meta-analyses were conducted to generate weighted group mean differences (WGMD) for between group comparisons (WP vs. other protein sources or carbohydrates) and within-WP group comparisons (i.e., differences from baseline to trial end). Studies were classified into two distinct groups—WP as a supplement without dietary modification (WPS) and WP as a replacement for other sources of calories (WPR)—and were meta-analyzed separately. Subgroup analyses included examining the effect of resistance exercise and type of WP on the relationship between WP and body composition.

Results: Fourteen RCTs were included, with a total of 626 adult study completers. Five studies examined the effects of WPR whereas the remaining nine studies examined the effects of WPS. Body weight (WGMD: -4.20kg, 95% CI: -7.67, -0.73) and body fat (WGMD: -3.74kg, 95% CI: -19 5.98, -1.50) were significantly decreased from baseline in the WPR within-group analyses. In the between-group analyses, the effects of WP were more favorable when compared with carbohydrates than protein sources other than whey, although findings did not reach statistical significance. Results from the subgroup analyses indicated a statistically significant increase in LBM (WGMD: 2.24 kg, 95% CI: 0.66, 3.81) among studies that included a resistance exercise component along with WP provision.

Conclusions: The current body of literature supports the use of WP, either as a supplement combined with resistance exercise or as part of a weight-loss or weight-maintenance diet, to improve body composition parameters.

Whooping cough bacterium evolves in Australia

The bacterium that causes whooping cough, Bordetella pertussis, has changed in Australia – most likely in response to the vaccine used to prevent the disease – with a possible reduced effectiveness of the vaccine as a result, a new study shows.

A UNSW-led team of researchers analysed strains of Bordetella pertussis from across Australia and found that many strains no longer produce a key surface protein called pertactin.

About 80 per cent of the 2012 whooping cough cases in Australia studied by the team were caused by pertactin-free strains. Pertactin is one of the three proteins, made from purified extracts of Bordetella pertussis bacteria, which are present in the vaccine currently used in Australia. The other two are pertussis toxin and filamentous haemagglutinin.

“It’s like a game of hide and seek. It is harder for the antibodies made by the body’s immune system in response to vaccination to ‘search and destroy’ the whooping cough bacteria which lack pertactin,” says the senior author of the study, Associate Professor Ruiting Lan, of the UNSW School of Biotechnology and Biomolecular Sciences.

“This could mean that these pertactin-free strains have gained a selective advantage over bacterial strains with the pertactin protein.”

The study is published in the journal Emerging Infectious Diseases.

Australia has only recently emerged from an epidemic of whooping cough that went on for an unusually long period – with about 142,000 cases from 2008 to 2012. Although the number of cases identified was greatly increased by more and better testing, the epidemic was still a major one. Nine babies died of whooping cough during the five years.

The research, led by UNSW PhD student Connie Lam, involved the analysis of 320 bacteria samples from patients with whooping cough obtained during 2008-2012 from five states – NSW, Victoria, Queensland, South Australia and Western Australia.

The proportion of pertactin-free bacteria rose from five per cent of cases tested in 2008 to 78 per cent in 2012. Pertactin-free strains of pertussis have also been detected overseas, including in countries such as France and the United States.

“The fact that they have arisen independently in different countries suggests this is in response to the vaccine,” says Associate Professor Lan.

There is no evidence that the pertactin-free strains are more harmful than other strains, and it is not yet clear whether they reduce the effectiveness of the vaccine in the short or long term.

“More studies are needed to better understand the effects of vaccination on the evolution of the organism,” says Associate Professor Lan.

The current acellular vaccine, purified down to three antigens, was introduced in 1997 to replace the previous whole-cell vaccine, after side effects such as fever and crying dissuaded many parents from starting or completing the three doses of vaccine required by six months of age.

“The acellular pertussis vaccine produces antibodies against pertussis toxin which is the main cause of severe disease symptoms produced by the whooping cough bacterium. Vaccination is still the only way to protect against whooping cough, especially for the youngest babies who are most at risk of severe illness,” stressed Associate Professor Lan.

Babies need to be immunised at six to eight weeks of age, four months and six months, with a booster at four years.

Johns Hopkins Bloomberg School of Public Health Researchers Find Association Between SSRI Use During Pregnancy and Autism and Developmental Delays in Boys

Highest Association Found During First Trimester Exposure for Autism and Third Trimester Exposure for Developmental Delays

In a study of nearly 1,000 mother-child pairs, researchers from the Bloomberg School of Public health found that prenatal exposure to selective serotonin reuptake inhibitors (SSRIs), a frequently prescribed treatment for depression, anxiety and other disorders, was associated with autism spectrum disorder (ASD) and developmental delays (DD) in boys. The study, published in the online edition of Pediatrics, analyzed data from large samples of ASD and DD cases, and population-based controls, where a uniform protocol was implemented to confirm ASD and DD diagnoses by trained clinicians using validated standardized instruments.

The study included 966 mother-child pairs from the Childhood Autism Risks from Genetics and the Environment (CHARGE) Study, a population-based case-control study based at the University of California at Davis’ MIND Institute. The researchers broke the data into three groups: Those diagnosed with autism spectrum disorder (ASD), those with developmental delays (DD) and those with typical development (TD). The children ranged in ages two to five. A majority of the children were boys – 82.5% in the ASD group were boys, 65.6% in the DD group were boys and 85.6% in the TD were boys. ” While the study included girls, the substantially stronger effect in boys alone suggests possible gender difference in the effect of prenatal SSRI exposure.

“We found prenatal SSRI exposure was nearly 3 times as likely in boys with ASD relative to typical development, with the greatest risk when exposure took place during the first trimester,” said Li-Ching Lee, Ph.D., Sc.M., psychiatric epidemiologist in the Bloomberg School’s Department of Epidemiology. “SSRI was also elevated among boys with DD, with the strongest exposure effect in the third trimester.”

The data analysis was completed by Rebecca Harrington, Ph.D., M.P.H, in conjunction with her doctoral dissertation at the Bloomberg School. Dr. Lee was one of her advisors.

Serotonin is critical to early brain development; exposure during pregnancy to anything that influences serotonin levels can have potential effect on birth and developmental outcomes. The prevalence of ADS continues to rise. According to the Centers for Disease Control and Prevention, an estimated 1 in 68 children in the U.S. is identified with ADS, and it is almost five times more common among boys than girls.  One may question whether the increased use of SSRI in recent years is a contributor to the dramatic rise of ASD prevalence.

“This study provides further evidence that in some children, prenatal exposure to SSRIs may influence their risk for developing an autism spectrum disorder,” said Irva Hertz-Picciotto, Ph.D., M.P.H., chief of the Division of Environmental and Occupational Health in the UC Davis Department of Public Health Sciences and a researcher at the UC Davis MIND Institute.  “This research also highlights the challenge for women and their physicians to balance the risks versus the benefits of taking these medications, given that a mother’s underlying mental-health conditions also may pose a risk, both to herself and her child.”

Regarding treatment, the authors note that maternal depression itself carries risks for the fetus, and the benefits of using SSRI during pregnancy should be considered carefully against the potential harm. The researchers also note that large sample studies are needed to investigate the effects in girls with ASD. Limitations of the study acknowledged include the difficulty in isolating SSRI effects from those of their indications for use, lack of information on SSRI dosage precluded dose-response analyses, and the relatively small sample of DD children resulted in imprecise estimates of association, which should be viewed with caution.

Prenatal SSRI Use and Offspring With Autism Spectrum Disorder or Developmental Delay” was written by Rebecca A. Harrington, PhD, MPH; Li-Ching Lee, PhD, ScM; Rosa M. Crum, MD, MHS; Andrew W. Zimmerman, MD; and Irva Hertz-Picciotto, PhD, MPH.

Data collection of this research was supported by U.S. National Institute of Environmental Health Sciences (NIEHS (#P01-ES11269 and #R01-ES015359), UC Davis MIND Institute and Autism Speaks.

# # #

Media contact for Johns Hopkins Bloomberg School of Public Health: Susan Sperry at 410-955-6919 or ssperry1@jhu.edu.

High disease load reduces mortality of children

Trans-generational defense mechanism in humans proved

Children who have been conceived during a severe epidemic are more resistant against other pathogens later in life. For the first time this has been proved by researchers at the Max Planck Institute for Demographic Research (MPIDR) in Rostock, Germany, for the 18th century epidemics of measles and smallpox in the Canadian province of Québec. Children who were conceived during the wave of measles in 1714 and 1715 died significantly less often from smallpox 15 years later than children who had been conceived before the measles epidemic. This is the result of a study published in the scientific journal PLOS ONE by Max Planck researcher Kai Willführ and Mikko Myrskylä from the London School of Economics and Political Science.

“We have proved that parents can essentially prepare their children for future diseases,” says bio-demographer Willführ. “The underlying mechanism is not purely genetic, nor is the children’s resistance restricted to single pathogens.” Scientists call such a transfer a “functional trans-generational effect.” Parents who faced an increased disease load during conception not only gave their children protection against this one infection, but the defence against pathogens apparently also worked better in the next generation against different illnesses like smallpox.

The moment of conception was critical for life or death for many children during the 1730 smallpox epidemic. The probability of dying from smallpox had dropped to less than 15 percent for children conceived during the measles epidemic in 1714 and 1715 compared to their brothers or sisters who had been conceived and born before the measles epidemic. But there was a high price to pay. Those children who were so resistant to smallpox survived the later epidemic with greater probability. But during the time between the two waves of epidemics, their mortality was three times that of their siblings who had been conceived before the earlier measles epidemic and thus were less resistant to smallpox.

“The way children’s bodies fight diseases seems to be optimized for a world with high pathogen load if it was also high at conception,” says MPIDR researcher Kai Willführ. But the children’s resistance does not fit into a world with fewer pathogens and works less well under normal circumstances.

“It was only during conception and pregnancy that measles could have given an advantage that parents passed on to the next generation,” says Kai Willführ. When the children conceived at the peak of the measles epidemic were born, the measles epidemic had already passed; the pathogens were no longer in the environment. It can be ruled out that children simply became immune. In principle it is possible for a mother to pass her antibodies, and thus immunity, to her baby. This happens through the placenta during pregnancy and through breast milk after birth. But this protection is limited to the same illness the mother had immunity against. In Québec this would have been measles. However, in this study the researchers found that the children were also resistant against another disease, namely smallpox. For the first time, the scientists could separate the mortality effects of the different diseases, because they traced the life course of each child individually and of their siblings. For their study they investigated birth cohorts from 1705 to 1724 and their mortality until the year 1740. They achieved data about births and deaths from transcriptions of old church registers of the historical population of the St. Lawrence River valley in the Canadian province of Québec.

 

In order to not be misidentified as spam, please mention something in the article.

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s