Health Technology Research Synopsis
121st Issue Date 27JAN2012
Compiled By Ralph Turchiano
Editors Top Five:
1. Compounds in mate tea induce death in colon cancer cells
2. ‘DIMming’ cancer growth — STAT: Diindolylmethane suppresses ovarian cancer
3. Pycnogenol (French maritime pine bark extract) shown to improve visible signs of aging
4. Grape seed extract kills head and neck cancer cells, leaves healthy cells unharmed
5. Bedwetting can be due to undiagnosed constipation, research shows
In this Issue:
1. Vitamin D could help combat the effects of aging in eyes
2. Effects of Tamiflu still uncertain, warn experts, as Roche continues to withhold key trial data
3. Is it the alcohol or polyphenols in red wine that decreases cardiovascular disease?
4. First link between potentially toxic PFCs in office air and in office workers’ blood
5. How drugs get those tongue-twisting generic names
6. Nursing home residents with dementia: Antidepressants are associated with increased risk of falling
7. Choking game prevalent among teens in Texas
8. Carnegie Mellon study reveals potential of manganese in neutralizing deadly Shiga toxin
9. PCE in drinking water linked to an increased risk of mental illness
10. Accelerated infant growth increases risk of future asthma symptoms in children
11. Exposure to chemical found in personal care products may contribute to childhood obesity
12. Autism redefined: Yale researchers study impact of proposed diagnostic criteria
13. UI study: High levels of MRSA bacteria in retail meat products
14. Plant flavonoid luteolin blocks cell signaling pathways in colon cancer cells
15. Enriched skimmed milk may curb frequency of gout flare-ups
16. Compounds in mate tea induce death in colon cancer cells
17. CU School of Medicine researchers look at effects of 2 common sweeteners on the body
18. More on legal remedies for ghostwriting
19. Study examines link between vaccinations and exposure to compound widely used in food packaging
20. Cocoa could prevent intestinal pathologies such as colon cancer
21. High fructose consumption by adolescents may put them at cardiovascular risk
22. ‘DIMming’ cancer growth — STAT: Diindolylmethane suppresses ovarian cancer
23. Pycnogenol (French maritime pine bark extract) shown to improve visible signs of aging in new study
24. Avastin, Sutent increase breast cancer stem cells, U-M study shows
25. IBD travelers are not at higher risk of contracting intestinal infections
26. New standard for vitamin D testing to ensure accurate test results
27. High animal fat diet increases gestational diabetes risk
28. Newly engineered highly transmissible H5N1 strain ignites controversy about balancing scientific discovery and public safety
29. NIH study shows caffeine consumption linked to estrogen changes
30. Grape seed extract kills head and neck cancer cells, leaves healthy cells unharmed
31. Bedwetting can be due to undiagnosed constipation, research shows
Vitamin D could help combat the effects of aging in eyes
Researchers funded by the Biotechnology and Biological Sciences Research Council (BBSRC) have found that vitamin D reduces the effects of ageing in mouse eyes and improves the vision of older mice significantly. The researchers hope that this might mean that vitamin D supplements could provide a simple and effective way to combat age-related eye diseases, such as macular degeneration (AMD), in people.
The research was carried out by a team from the Institute of Ophthalmology at University College London and is published in the current issue of the journal Neurobiology of Ageing.
Professor Glen Jeffery, who led the work, explains “In the back of the eyes of mammals, like mice and humans, is a layer of tissue called the retina. Cells in the retina detect light as it comes into the eyes and then send messages to the brain, which is how we see. This is a demanding job, and the retina actually requires proportionally more energy than any other tissue in the body, so it has to have a good supply of blood. However, with ageing the high energy demand produces debris and there is progressive inflammation even in normal animals. In humans this can result in a decline of up to 30% in the numbers of light receptive cells in the eye by the time we are 70 and so lead to poorer vision.”
The researchers found that when old mice were given vitamin D for just six weeks, inflammation was reduced, the debris partially removed, and tests showed that their vision was improved.
The researchers identified two changes taking place in the eyes of the mice that they think accounted for this improvement. Firstly, the number of potentially damaging cells, called macrophages, were reduced considerably in the eyes of the mice given vitamin D. Macrophages are an important component of our immune systems where they work to fight off infections. However in combating threats to the aged body they can sometimes bring about damage and inflammation. Giving mice vitamin D not only led to reduced numbers of macrophages in the eye, but also triggered the remaining macrophages to change to a different configuration. Rather than damaging the eye the researchers think that in their new configuration macrophages actively worked to reduce inflammation and clear up debris.
The second change the researchers saw in the eyes of mice given vitamin D was a reduction in deposits of a toxic molecule called amyloid beta that accumulates with age. Inflammation and the accumulation of amyloid beta are known to contribute, in humans, to an increased risk of age-related macular degeneration (AMD), the largest cause of blindness in people over 50 in the developed world. The researchers think that, based on their findings in mice, giving vitamin D supplements to people who are at risk of AMD might be a simple way of helping to prevent the disease.
Professor Jeffery said “When we gave older mice the vitamin D we found that deposits of amyloid beta were reduced in their eyes and the mice showed an associated improvement of vision. People might have heard of amyloid beta as being linked to Alzheimer’s disease and new evidence suggests that vitamin D could have a role in reducing its build up in the brain. So, when we saw this effect in the eyes as well, we immediately wondered where else these deposits might be being reduced.”
Professor Jeffery and his team then went on to study some of the blood vessels of their mice. They found that the mice that had been given the vitamin D supplement also had significantly less amyloid beta built up in their blood vessels, including in the aorta.
Professor Jeffery continues “Finding that amyloid deposits were reduced in the blood vessels of mice that had been given vitamin D supplements suggests that vitamin D could be useful in helping to prevent a range of age-related health problems, from deteriorating vision to heart disease.”
Professor Jeffery thinks that this link between vitamin D and a range of age-related diseases might be linked to our evolutionary history. For much of human history our ancestors lived in Africa, probably without clothes, and so were exposed to strong sunlight all year round. This would have triggered vitamin D production in the skin. Humans have only moved to less sunny parts of the world and adopted clothing relatively recently and so might not be well adapted to reduced exposure to the sun. Secondly, life expectancy in the developed world has increased greatly over the past few centuries, so reduced exposure to vitamin D is now coupled with exceptionally long lifespan.
Professor Jeffery said “Researchers need to run full clinical trials in humans before we can say confidently that older people should start taking vitamin D supplements, but there is growing evidence that many of us in the Western world are deficient in vitamin D and this could be having significant health implications.”
Professor Douglas Kell, BBSRC Chief Executive said “Many people are living to an unprecedented old age in the developed world. All too often though, a long life does not mean a healthy one and the lives of many older people are blighted by ill health as parts of their bodies start to malfunction.
“If we are to have any hope of ensuring that more people can enjoy a healthy, productive retirement then we must learn more about the changes that take place as animals age. This research shows how close study of one part of the body can lead scientists to discover new knowledge that is more widely applicable. By studying the fundamental biology of one organ scientists can begin to draw links between a number of diseases in the hope of developing preventive strategies.”
Effects of Tamiflu still uncertain, warn experts, as Roche continues to withhold key trial data
2 years after pharmaceutical giant Roche promised the BMJ it would release key Tamiflu trial data for independent scrutiny, the safety and effectiveness of this anti-influenza drug remains uncertain, warn experts today
Two years after pharmaceutical giant Roche promised the BMJ it would release key Tamiflu trial data for independent scrutiny, the safety and effectiveness of this anti-influenza drug remains uncertain, warn experts today.
A new report by the Cochrane Collaboration says Roche’s refusal to provide full access to all its data leaves critical questions about how well the drug works unresolved.
A BMJ investigation, published to coincide with today’s report, also raises serious concerns about access to drug data, the use of ghost writers in drug trials, and the drug approval process.
Meanwhile, Tamiflu has become the mainstay of influenza treatment in the UK. It has also made it onto the World Health Organisation’s list of Essential Medicines and Roche’s claims continue to be supported by influential health agencies.
The Cochrane researchers set out to test Roche’s claim that Tamiflu prevented complications and reduced the number of people needing hospital treatment. But their investigation was hampered by Roche’s refusal to provide all of its trial data for analysis. The team obtained some clinical study reports from the European Medicines Agency (EMA), but found inconsistencies with published reports and possible under-reporting of side effects.
When previously questioned by the BMJ, Roche also admitted that some of the published papers had been ghost written.
The BMJ investigation reveals how different regulators took different approaches to the data submitted to them, leading to conflicting messages about it effectiveness.
For example, the EMA released a proportion of the clinical study reports relating to the Tamiflu trials to Cochrane, but it admits that it did not ask for the remainder from the manufacturer, although it was legally entitled to do so. The EMA has since told the BMJ that it plans to start publishing reports for all drugs submitted for approval in the next few years.
Dr Fiona Godlee, BMJ Editor-in-Chief says: “We hope very much that the EMA will indeed take this important step in making the full study reports available. But we are still a long way away from having a full trial history for all drugs in clinical use. Public safety and the proper use of public money demands that we should stop at nothing less than this.”
Meanwhile, the US Food and Drug Administration (FDA), which has reviewed the Tamiflu trial programme in perhaps more detail than anyone outside of Roche, chose not to review the largest ever trial of Tamiflu when considering the drug for approval. It states that “Tamiflu has not been shown to prevent such complications [serious bacterial infections].”
However, the US Centers for Disease Control and Prevention (CDC) continue to cite key published trials of Tamiflu, claiming a reduced risk of influenza complications, even after Roche admitted that some of these trials have been ghost written.
Dr Godlee says: “The discrepancies between the conclusions reached by different regulators around the world highlights the absurd situation we find ourselves in. In a globalised world, regulators should cooperate and pool their limited resources. Otherwise we will continue to waste money and risk people’s health on drugs that don’t work.”
The investigation also raises questions about Tamiflu’s clinical effects. After careful evaluation of trial data, the Cochrane group say that Tamiflu appears to affect antibody production – a claim that Roche refutes. This is important, say Cochrane, because influenza vaccination relies on an antibody response to be effective. But when asked by the BMJ, Roche refused to explain how the drug works.
As such, the Cochrane group say that “until more is known about the mode of action of neuraminidase inhibitors, health professionals, patients and other decision makers need to reflect on the findings of this review before making any decision about the use of the drug.”
Cochrane also argue that Tamiflu’s ability to prevent the spread of influenza has not been demonstrated in trials. Yet this is one of the main reasons governments around the world have spent billions of dollars stockpiling Tamiflu in case of a pandemic.
Roche maintain they provided the Cochrane team with enough information to conduct their evaluation, but the Cochrane team say this is not the case. Dr Peter Doshi from Johns Hopkins University School of Medicine says: “In the BMJ in December 2009, Roche promised full study reports to any legitimate investigators. They have not provided a single full study report to Cochrane, despite our repeated requests.”
Is it the alcohol or polyphenols in red wine that decreases cardiovascular disease?
Observational epidemiologic studies relating wine and alcohol to health all suffer from the fact that they, of necessity, compare people who prefer certain beverages, but not the beverages themselves. While there have been many intervention trials in animals, randomized trials in humans are less common. Randomized crossover trials, in which each subject receives all interventions in sequence, can be especially important as they tend to avoid baseline differences among subjects and can detect effects of different interventions with smaller numbers of subjects.
This study by Chiva-Blanch G et al, just published in the American Journal of Clinical Nutrition, included 67 male volunteers in Spain who were considered to be at “high-risk” of cardiovascular disease on the basis of increased BMI, smoking, diabetes, hypertension, or other risk factors. About one half of the individuals were taking ACE inhibitors, statins, aspirin, and/or oral hypoglycemic drugs, so the results of this study may be especially relevant for patients in the real world.
The subjects agreed to not consume any alcohol for a baseline period, then for three one-month periods consumed 30 g/day of alcohol as red wine or as gin, or an equivalent amount of phenolics from dealcoholized red wine. The polyphenol contents of the RW and the DRW interventions were the same. A very high degree of compliance of the subjects with the assigned interventions is evidenced by results of counting numbers of empty bottles of the intervention beverage returned, dietary records, urinary metabolites, etc. Further, there is good evidence that there were no important changes between periods in diet or exercise habits. The effects of each intervention on a large number of adhesion molecules and chemokines that affect inflammation and relate to the development of vascular disease were evaluated.
The key results of the study were that both ethanol and nonalcoholic compounds in red wine have potentially protective effects that may reduce the risk of vascular disease. Specifically, the authors conclude that “the phenolic content of red wine may modulate leukocyte adhesion molecules, whereas both ethanol and polyphenols of red wine may modulate soluble inflammatory mediators in patients at high risk of cardiovascular disease.”
Specific comments on the study: Most reviewers considered this to be a well-done, comprehensive study. As one reviewer commented: “This is an excellent paper. The results strongly indicate an effect of wine polyphenols on inflammation (in broad and modern terms) and this is just what we expect from the biochemistry and nutritional effects of fruits and vegetables. The effect of ethanol, on the other hand, likely fits a hormetic mechanism, where low doses regularly supplied are protective while high doses in a single shot are worsening the progression of disease.” Another reviewer added: “We need more information on separating the effects of beer, wine, and various types of spirits. Some spirits like brandy and whisky can have useful antioxidant effects, so distinguishing effects among different types of beverages may be informative.”
Another Forum reviewer commented: “This is a very interesting paper that goes a way towards answering the question whether it is the alcohol or polyphenols in red wine that confer the health benefits. The trial was well conducted and controlled, with very detailed analyses. It would have been interesting to analyse any changes in conventional risk factors after the interventions. It would also have been interesting in the study to determine the effects on vascular function by, for example, brachial artery activity (flow mediated dilatation).”
Given that the effects of both alcohol and polyphenols on physiologic factors (e.g., platelet function, fibrinolysis) are transient, generally lasting for no more than 24 hours, it was appropriate that the subjects in this study were instructed to consume the intervention substance (RW, gin, DRW) on a daily basis. When drinking is moderate, there is no evidence that having “alcohol-free days” is beneficial to health. Indeed, most epidemiologic studies show better health effects from daily consumption rather than from drinking on a few days per week.
Concerns about the present study: One Forum reviewer stated: “This appears to be a carefully designed and well executed study, but I have four concerns: (1) The study has been undertaken in high-risk individuals, more than half of whom are hypertensive, a quarter dyslipidaemic, and a quarter diabetic. It is not described what happened to the conventional risk factors during the interventions. (For example, any improvement in inflammatory markers may have come at the cost of higher blood pressure with the alcohol interventions.) (2) Was there any weight change that could have confounded any of the outcomes? (3) Both polyphenol and alcohol biomarkers were measured – did the change in these biomarkers correlate with the changes in any of the inflammatory markers; i.e., any suggestion of a dose response relationship? (4) Even though at least 30 outcome variables were assessed, the authors do not describe any correction for multiple comparisons.”
Another Forum reviewer: “This is a well conducted study, and adds to our understanding of the potential cardiovascular benefits of alcohol and the non-alcoholic compounds of alcoholic beverages. However, in this study more than one-half of the high-risk subjects consumed drugs with known anti-inflammatory effects, which could be a confounding factor. The anti-inflammatory effects of these pharmaceuticals may be responsible for the beneficial results, and may not be related to the RW, DRW and gin interventions.” However, others think that this concern is unlikely to be important since this was a crossover study, and there were no changes in lifestyle or medication use between the intervention periods.
The key results of the study were that both ethanol and nonalcoholic compounds in red wine have potentially protective effects that may reduce the risk of vascular disease. Specifically, the authors conclude that “the phenolic content of red wine may modulate leukocyte adhesion molecules, whereas both ethanol and polyphenols of red wine may modulate soluble inflammatory mediators in patients at high risk of cardiovascular disease.” Thus, this study provides important new mechanistic evidence that the reduced risk of cardiovascular disease among red wine drinkers observed in most epidemiologic studies may result from a combination of both the alcohol and the polyphenols in the wine.
First link between potentially toxic PFCs in office air and in office workers’ blood
In a first-of-its-kind study, scientists are reporting that the indoor air in offices is an important source of worker exposure to potentially toxic substances released by carpeting, furniture, paint and other items. Their report, which documents a link between levels of these so-called polyfluorinated compounds (PFCs) in office air and in the blood of workers, appears in ACS’ journal Environmental Science & Technology.
Michael McClean and colleagues explain that PFCs, used in water-repellent coatings on carpet and furniture, may have adverse effects on human health. The substances are widespread in the environment and in humans around the world. Scientists know that potential sources of exposure include food, water, indoor air, indoor dust and direct contact with PFC-containing objects. But the link between levels in air and blood had not been explored previously, so McClean’s group set out to fill that gap with a study of 31 office workers in Boston.
They found concentrations of a PFC called fluorotelomer alcohol (FTOH) in office air that were 3-5 times higher than those reported in previous studies of household air, “suggesting that offices may represent a unique and important exposure environment.” In addition, the study found a strong link between concentrations of FTOH in office air and perfluorooctanoic acid (a metabolite of FTOH) in the blood of office workers. The results also suggested that workers in newly renovated office buildings may receive considerably higher doses of PFCs than workers in older buildings.
How drugs get those tongue-twisting generic names
Oseltamivir. Esomeprazole. Trastuzumab. Where do drugs get those odd-sounding generic names? The answers are in the current issue of Chemical & Engineering News (C&EN), the weekly newsmagazine of the American Chemical Society, the world’s largest scientific society, which explains the logic behind the tongue-twisters.
C&EN Associate Editor Carmen Drahl explains that until 1961 there was no standard for assigning drugs generic names, which are different from brand names like Tamiflu (oseltamivir), Nexium (esomeprazole) and Herceptin (trastuzumab). That’s when three medical organizations created the U.S. Adopted Names (USAN) Council to assign simplified alternatives to the unwieldy proper names the International Union of Pure & Applied Chemistry gives to molecules. For instance, under USAN’s guidance, “cis-8-methyl-N-vanillyl-6-nonenamide” becomes “zucapsaicin.” The council recommends generic names to an international agency of the World Health Organization. The tongue-twisting words the USAN Council creates are products of “stems” that describe a drug’s characteristics, which Drahl likens to the Latin and Greek roots of many English words.
Drahl writes that these stems describe everything from a drugs’ function to its shape. For instance, the “-prazole” ending of Nexium’s generic name, esomeprazole, reveals that it is a type of antiulcer medication. Similar drugs will have the same stems in their names, allowing those familiar with the stems to crack the code. The USAN Council is careful to avoid words that are difficult to pronounce in foreign languages or that may have other meanings abroad. Sometimes, Drahl notes, a generic name will also include hints about its developer that a drug company has suggested to the council, as in carfilzomib, which recognizes molecular biologist Philip Whitcome and his wife Carla.
Nursing home residents with dementia: Antidepressants are associated with increased risk of falling
Nursing home residents with dementia who use average doses of selective serotonin reuptake inhibitors (SSRIs) are three times more likely to have an injurious fall than similar people who don’t use these drugs. The association can be seen in people who use low doses of SSRIs and the risk increases as people take higher doses. The results are published in the British Journal of Clinical Pharmacology.
Many nursing home residents with dementia suffer from depression, and are therefore treated with antidepressants. Selective serotonin reuptake inhibitors (SSRIs) are generally considered the treatment of choice. “Our study also discovered that the risk of an injurious fall increased even more if the residents were also given hypnotic or sedative drugs as sleeping pills,” said lead author Carolyn Shanty Sterke, who works in the Section of Geriatric Medicine at Erasmus University Medical Center, Rotterdam, The Netherlands.
Falls are a major health problem in nursing home residents with dementia. In nursing homes one-third of all falls result in an injury. “Physicians should be cautious in prescribing SSRIs to older people with dementia, even at low doses,” says Sterke.
Sterke carried out this research by recording the daily drug use and daily falls in 248 nursing home residents with dementia from 1 January 2006 until 1 January 2008. Data about the residents’ day-by day drug use came from a prescription database, and information on falls and subsequent injuries came from a standardised incident report system. In total, she had collected a dataset of 85,074 person-days.
The mean age of the participants was 82 years, and the prescription records showed that antidepressants had been used on 13,729 (16.1%) days, with SSRIs being used on 11,105 of these days.
The incident reports showed that 152 of the 248 residents (61.5%) sustained 683 falls. This corresponds to a fall incidence of 2.9 falls per person-year. Thirty-eight residents had a single fall, but 114 fell frequently. Two hundred twenty falls resulted in injury or death. Of these 10 were hip fractures, 11 were other fractures and 198 were injuries such as grazes, open wounds, sprains, bruises, and swellings. One person died after falling.
The risk of having an injurious fall increased threefold for residents taking SSRIs, from an absolute daily risk of 0.09% for a female aged 80 not taking an SSRI, to 0.28% for a female aged 80 taking one defined daily dose of SSRIs. Similar increases in absolute daily risk were found for both men and women, for different ages.
“Staff in residential homes are always concerned about reducing the chance of people falling and I think we should consider developing new treatment protocols that take into account the increased risk of falling that occurs when you give people SSRIs,” says Sterke.
Choking game prevalent among teens in Texas
Nearly one out of seven college students surveyed at a Texas university has participated in the Choking Game, a dangerous behavior where blood flow is deliberately cut off to the brain in order to achieve a high, according to a study by The Crime Victims’ Institute at Sam Houston State University.
The Choking Game, also known as the Fainting Game, Pass Out, or Space Monkey, is played individually or in groups and involves manually choking oneself or others, applying a ligature around the neck or a plastic bag over the head, placing heavy objects on the chest, or hyperventilating to attain a euphoric feeling. This practice has led to several suffocation deaths in Texas and across the country.
“This study was undertaken to determine who is playing the game, in what context, and how they learned about it,” said Dr. Glen Kercher, director of the Crime Victims’ Institute. “It is our hope that these findings will inform efforts by parents, schools, and community agencies to warn young people about the dangers of participating in the Choking Game.”
The study was based on a survey completed by 837 students at a Texas university. Among the findings were:
16% percent of students reported having played the game; 72% reportedly played the game more than once
Males were more likely to have played than females
The average age when students first played the game was 14
90% of those who played the game first heard about it from peers
Most students reported that others were present when they first played the game
Curiosity about the effects of the Choking Game was a primary motivation for playing the game
Learning about the potential dangers in engaging in this activity served as a deterrent for the majority of non-participants.
“Even though awareness of the Choking Game is growing, it should be noted that encouragement for parents to discuss this activity with their children should still be stressed,” said Brittany Longino Smith, who co-authored the study “The Choking Game” with Dr. Kercher and Dr. Leana Bouffard, an Associate Professor at SHSU.
A similar study on the Choking Game found that 90 percent of parents would support incorporating information on the behavior in health and drug prevention classes.
While preventative programs have increased to help warn adolescents of the use of illegal substances, the Choking Game is another method of achieving similar effects that has been introduced to this age group. “This ‘game,’ as it is often called, does not require obtaining any drugs or alcohol, is free, and can go undetected by many parents, teachers, physicians, and other authority figures. Most importantly, many of those who engage in this activity, do not understand that the practice can be just as deadly as the illegal substances youth have been warned against,” the study found.
Carnegie Mellon study reveals potential of manganese in neutralizing deadly Shiga toxin
Findings could provide basis for first treatment for Shiga toxin infection
IMAGE:In early endosomes, Shiga toxin (green) is sorted into membrane tubules, which pinch off and move to the Golgi apparatus. The membrane left behind, marked by epidermal growth factor (red),…
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PITTSBURGH—Carnegie Mellon University researchers have discovered that an element commonly found in nature might provide a way to neutralize the potentially lethal effects of a compound known as Shiga toxin. New results published in the Jan. 20 issue of Science by Carnegie Mellon biologists Adam Linstedt and Somshuvra Mukhopadhyay show that manganese completely protects against Shiga toxicosis in animal models.
Produced by certain bacteria, including Shigella and some strains of E. coli, Shiga toxin can cause symptoms ranging from mild intestinal disease to kidney failure. The findings could pave the way for future research aimed at creating an inexpensive treatment for infections caused by bacteria that produce the lethal Shiga toxin. Currently there is no treatment for such infections that afflict more than 150 million people each year, resulting in more than one million deaths worldwide.
Such infections are common in developing countries where it causes waterborne epidemics. It can be particularly deadly, especially in children, as it causes dysentery and severe hemorrhagic diarrhea, which cannot be adequately treated in areas without access to clean water. In developed countries, Shiga toxicosis is most common during foodborne outbreaks — like the widespread E. coli outbreak this past summer in Germany and Western Europe, where more than 3,700 people were infected and 45 died.
After entering the body, Shiga toxin is secreted by the infecting bacteria. It then attaches itself to a surface receptor on a cell’s plasma membrane and enters the cell through a process called endocytosis. Normally, when a harmful substance enters a cell in this way, it’s wrapped in a package called an endosome and sent directly to the cell’s lysosome where it is degraded and discarded.
“That’s exactly the process that Shiga toxin avoids. It would be neutralized if it were to get degraded, so it had to find some way to get out of being sent to the lysosome,” said Linstedt, professor of biological sciences at Carnegie Mellon.
Linstedt and Mukhopadhyay discovered exactly how Shiga toxin avoided the lysosome as they were doing basic biological research to understand how components of the cell function. “If we weren’t focused on answering fundamental biological questions, we wouldn’t have made this discovery,” Linstedt said.
Fifteen years ago Linstedt discovered GPP130, a protein found in the Golgi apparatus, a kind of post office for the cell that sorts and packages molecules made in the endoplasmic reticulum and delivers them to their final destinations within the cell. GPP130, Linstedt found, didn’t behave like most Golgi proteins. Rather than remaining in the Golgi, GPP130 constantly cycles to the endosomes and back to the Golgi. As it returns, it avoids the pathway that takes a substance to the lysosome to be degraded.
In Science, Linstedt and Mukhopadhyay report that Shiga toxin exploits this unique quality of GPP130 to its advantage. As it starts its return to the Golgi, GPP130 moves into a tubular extension off of the endosome’s membrane and avoids being sent to the degradation pathway. Shiga toxin binds to GPP130, hitching a ride on a route that doesn’t go to the lysosome. Instead, the toxin is carried to the Golgi apparatus and then to the endoplasmic reticulum, where it gets released into the cell’s cytoplasm. It’s here that it does its damage, shutting down protein synthesis and causing the cell to die.
“I knew that Shiga toxin was one of the key cargo molecules that bypass the lysosome as they go from the endosome to the Golgi apparatus, so I figured it would be a good marker to study in relation to GPP130. What I didn’t realize was how profoundly dependent Shiga toxin was on GPP130,” Linstedt said.
VIDEO:In control cells, GPP130 cycles from the Golgi to endosomes and back. After internalization into endosomes, Shiga toxin binds GPP130 and is sorted into endosome membrane tubules that break…
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But the most serendipitous aspect of this discovery can be traced to a phone call made four years ago. Don Smith, a toxicologist at the University of California, Santa Cruz, who was studying manganese toxicity, noticed that GPP130 was sensitive to manganese. He called Linstedt who began to do a series of experiments on how manganese affects GPP130. Around this time Mukhopadhyay joined Linstedt’s lab for his post-doctoral training. He quickly discovered that as concentrations of manganese rise inside the cell, GPP130 changes its pathway and goes directly to the lysosome where it is degraded.
Because Shiga toxin was dependent on GPP130 and manganese caused loss of GPP130, Linstedt and Mukhopadhyay decided to see whether manganese would protect against Shiga toxin infection. In cell cultures, manganese treatment yielded an almost 4,000-fold increase in the amount of Shiga toxin required to induce cell death. In a mouse model, mice exposed to a high dose of Shiga toxin and treated with non-toxic doses of manganese were 100 percent resistant to the toxin.
By introducing manganese, Linstedt and Mukhopadhyay were able to remove Shiga toxin’s vehicle for avoiding degradation — GPP130. The researchers feel that this could be a promising treatment for neutralizing the effects of Shiga toxin in humans.
“Manganese is inexpensive. While Shiga toxin infection affects people in the developed world, it affects far more people in the developing world. An inexpensive, accessible treatment — not a designer drug — is the ideal solution,” Linstedt said. “We know the toxicity levels of manganese in humans; we know ways to administer it. While further testing is needed to determine if manganese is a suitable treatment for humans, I’m optimistic that trials should move forward quickly.”
The researchers also believe that manganese might be able to be used in conjunction with antibiotics. Currently, if an infected person is given an antibiotic, the antibiotic kills the bacteria (E. coli or Shigella) that produce the toxin. This releases the toxin in larger amounts and causes a higher percentage of patients to die. Linstedt believes that they can use manganese to block the toxin and an antibiotic to kill the bacteria, making for an extremely effective therapy.
The Carnegie Mellon researchers plan to continue their research by using situations that more closely mimic Shiga toxin infection in humans, and by testing their antibiotic/manganese combination therapy in mouse models. The researchers also will pay attention to manganese toxicity. High doses of manganese can have severe neurotoxic effects. The amounts used in the current study were low enough that they didn’t cause any side effects in the mouse models.
PCE in drinking water linked to an increased risk of mental illness
PCE in drinking water linked to an increased risk of mental illness
The solvent tetrachloroethylene (PCE) widely used in industry and to dry clean clothes is a neurotoxin known to cause mood changes, anxiety, and depression in people who work with it. To date the long-term effect of this chemical on children exposed to PCE has been less clear, although there is some evidence that children of people who work in the dry cleaning industry have an increased risk of schizophrenia. New research published in BioMed Central’s open access journal Environmental Health found that exposure to PCE as a child was associated with an increased risk of bipolar disorder and post traumatic stress disorder (PTSD).
From 1968, until the early 1980s, water companies in Massachusetts installed vinyl-lined (VL/AC) water pipes that were subsequently found to be leaching PCE into the drinking water supply. Researchers from Boston University followed the incidence of mental illness amongst adults from Cape Cod, born between 1969 and 1983, who were consequently exposed to PCE both before birth and during early childhood.
While there was no increase seen in the incidence of depression, regardless of PCE exposure, people with prenatal and early childhood exposure to PCE had almost twice the risk of bipolar disorder, compared to an unexposed group, and their risk of PTSD was raised by 50%.
Dr Ann Aschengrau from Boston University School of Public Health warned, “It is impossible to calculate the exact amount of PCE these people were exposed to – levels of PCE were recorded as high as 1,550 times the currently recommended safe limit. While the water companies flushed the pipes to address this problem, people are still being exposed to PCE in the dry cleaning and textile industries, and from consumer products, and so the potential for an increased risk of illness remains real.”
Accelerated infant growth increases risk of future asthma symptoms in children
Accelerated growth in the first three months of life, but not fetal growth, is associated with an increased risk of asthma symptoms in young children, according to a new study from The Generation R Study Group at Erasmus Medical Center in the Netherlands.
“We know that low birth weight is associated with an increased risk of asthma symptoms in children, but the effects of specific fetal and infant growth patterns on this risk had not been examined yet,” said researcher Liesbeth Duijts, MD, PhD. “In our study, weight gain acceleration in early infancy was associated with an increased risk of asthma symptoms in children of preschool age, independent of fetal growth patterns, suggesting that early infancy might be a critical period for the development of asthma.”
The findings were published online ahead of print publication in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.
This study was embedded in the Generation R Study, a population-based prospective cohort study, and included 5,125 children who were followed from fetal life through the age of four. Information on asthma symptoms was obtained by questionnaires at the ages of 1, 2, 3, and 4.
No consistent relationships between fetal length and weight growth during different trimesters and the development of asthma symptoms were observed. Accelerated weight gain from birth to 3 months following normal fetal growth was associated with increased risks of asthma symptoms, including wheezing (overall odds ratio (OR) 1.44 (95% confidence interval (CI): 1.22, 1.70), shortness of breath: 1.32 (1.12, 1.56), dry cough: 1.16 (1.01, 1.34), and persistent phlegm: 1.30 (1.07, 1.58)). The associations between accelerated infant growth and risk of developing asthma symptoms were independent of other fetal growth patterns and tended to be stronger among children of atopic mothers.
“Our results suggest that the relationship between infant weight gain and asthma symptoms is not due to the accelerated growth of fetal growth-restricted infants only,” said Dr. Duijts. “While the mechanisms underlying this relationship are unclear, accelerated weight growth in early life might adversely affect lung growth and might be associated with adverse changes in the immune system.”
The study had a few limitations, including the possibility of measurement error in the estimation of fetal weight and the use of self-report for asthma symptoms.
“Further research is needed to replicate our findings and explore the mechanisms that contribute to the effects of growth acceleration in infancy on respiratory health,” concluded Dr. Duijts. “The effects of infant growth patterns on asthma phenotypes in later life should also be examined.”
Exposure to chemical found in personal care products may contribute to childhood obesity
Researchers from the Children’s Environmental Health Center at The Mount Sinai Medical Center in New York have found an association between exposure to the chemical group known as phthalates and obesity in young children – including increased body mass index (BMI) and waist circumference.
Phthalates are man-made, endocrine-disrupting chemicals that can mimic the body’s natural hormones. They are commonly used in plastic flooring and wall coverings, food processing materials, medical devices, and personal-care products. While poor nutrition and physical inactivity are known to contribute to obesity, a growing body of research suggests that environmental chemicals – including phthalates – could play a role in rising childhood obesity rates.
This study was the first to examine the relationship between phthalate exposure and measurements used to identify obesity in children. The paper is available online in the journal Environmental Research. The project was funded by the National Institute for Environmental Health Sciences, the National Cancer Institute, and the U.S. Environmental Protection Agency.
Mount Sinai researchers measured phthalate concentrations in the urine of 387 black and Hispanic children in New York City, and recorded body measurements including BMI, height, and waist circumference one year later. The urine tests revealed that greater than 97 percent of study participants had been exposed to phthalates typically found in personal care products such as perfume, lotions, and cosmetics; varnishes; and medication or nutritional supplement coatings. The phthalates included monoethyl phthalate (MEP) and other low molecular-weight phthalates. The team also found an association between concentrations of these phthalates with BMI and waist circumference among overweight children. For example, BMI in overweight girls with the highest exposure to MEP was 10 percent higher than those with the lowest MEP exposure.
“Research has shown that exposure to these everyday chemicals may impair childhood neurodevelopment, but this is the first evidence demonstrating that they may contribute to childhood obesity,” said the study’s lead author Susan Teitelbaum, PhD, Associate Professor in the Department of Preventive Medicine at Mount Sinai School of Medicine. “This study also further emphasizes the importance of reducing exposure to these chemicals where possible.”
The percentage of obese children ages six to 11 in the United States has grown from seven percent in 1980 to more than 40 percent in 2008, according to the U.S. Centers for Disease Control and Prevention. More than 15 percent of American children between the ages six and 19 are characterized as obese. In New York City, more than one in five children in public schools are obese.
Dr. Teitelbaum and the team at the Children’s Environmental Health Center plan to further evaluate the impact of these chemicals on childhood obesity. “While the data are significant, more research is needed to definitively determine whether phthalate exposure causes increases in body size,” she said.
Autism redefined: Yale researchers study impact of proposed diagnostic criteria
By Karen N. Peart
January 20, 2012
Helping an autistic child develop a “visual queue” to guide him through daily life.
Getting an autism diagnosis could be more difficult in 2013 when a revised diagnostic definition goes into effect. The proposed changes may affect the proportion of individuals who qualify for a diagnosis of autism spectrum disorder, according to preliminary data presented by Yale School of Medicine researchers at a meeting of the Icelandic Medical Association.
The proposed changes to the diagnostic definition would be published in the fifth edition of the American Psychiatric Association’s (APA) “Diagnostic and Statistical Manual of Mental Disorders (DSM-5).”
“Given the potential implications of these findings for service eligibility, our findings offer important information for consideration by the task force finalizing DSM-5 diagnostic criteria,” said Yale Child Study Center (CSC) director Fred Volkmar, M.D., who conducted the study with CSC colleagues Brian Reichow and James McPartland.
Volkmar and his team found that in a group of individuals without intellectual disabilities who were evaluated during the 1994 DSM-IV field trial, it was estimated that approximately half might not qualify for a diagnosis of autism under the proposed new definition.
Volkmar stressed that these preliminary findings relate only to the most cognitively able and may have less impact on diagnosis of more cognitively disabled people. “Use of such labels, particularly in the United States, can have important implications for service,” he said. “Major changes in diagnosis also pose issues for comparing results across research studies.”
Volkmar first presented the preliminary research results in September at Yale and in October at the Institute On Autism American Academy of Child Adolescent Psychiatry Meeting In Toronto. Volkmar and colleagues will publish full study results in the April print edition of the Journal of the American Academy of Child and Adolescent Psychiatry. The study may be available online as early as late February or early March.
Ralphs Note: What a lousy way to cover up an epidemic….
UI study: High levels of MRSA bacteria in retail meat products
Retail pork products in the United States. have a higher prevalence of methicillin-resistant Staphylococcus aureus bacteria (MRSA) than previously identified, according to new research by the University of Iowa College of Public Health and the Institute for Agriculture and Trade Policy.
MRSA can occur in the environment and in raw meat products, and is estimated to cause around 185,000 cases of food poisoning each year. The bacteria can also cause serious, life-threatening infections of the bloodstream, skin, lungs, and other organs. MRSA is resistant to a number of antibiotics.
The study, published Jan. 19 in the online science journal PLoS ONE, represents the largest sampling of raw meat products for MRSA contamination to date in the U.S. The researchers collected 395 raw pork samples from 36 stores in Iowa, Minnesota, and New Jersey. Of these samples, 26 — or about 7 percent — carried MRSA.
“This study shows that the meat we buy in our grocery stores has a higher prevalence of staph than we originally thought,” says lead study author Tara Smith, Ph.D., interim director of the UI Center for Emerging and Infectious Diseases and assistant professor of epidemiology. “With this knowledge, we can start to recommend safer ways to handle raw meat products to make it safer for the consumer.”
The study also found no significant difference in MRSA contamination between conventional pork products and those raised without antibiotics or antibiotic growth promotants.
“We were surprised to see no significant difference in antibiotic-free and conventionally produced pork,” Smith says. “Though it’s possible that this finding has more to do with the handling of the raw meat at the plant than the way the animals were raised, it’s certainly worth exploring further.”
Plant flavonoid luteolin blocks cell signaling pathways in colon cancer cells
Plant flavonoid luteolin blocks cell signaling pathways in colon cancer cells
Luteolin is a flavonoid commonly found in fruit and vegetables. This compound has been shown in laboratory conditions to have anti-inflammatory, anti-oxidant and anti-cancer properties but results from epidemiological studies have been less certain. New research published in BioMed Central’s open access journal BMC Gastroenterology shows that luteolin is able to inhibit the activity of cell signaling pathways (IGF and PI3K) important for the growth of cancer in colon cancer cells.
Colon cancer is the second most frequent cause of cancer-related death in the Western World. Colon cancer cells have elevated levels of IGF-II compared to normal colon tissues. It is thought that this is part of the mechanism driving uncontrolled cell division and cancer growth. Researchers from Korea showed that luteolin was able to block the secretion of IGF-II by colon cancer cells and within two hours decreased the amount of receptor (IGF-IR) precursor protein. Luteolin also reduced the amount of active receptor (measured by IGF-I dependent phosphorylation).
Luteolin inhibited the growth stimulatory effect of IGF-I and the team led by Prof Jung Han Yoon Park found that luteolin affected cell signaling pathways which are activated by IGF-I in cancer. Prof Jung Han Yoon Park explained, “Luteolin reduced IGF-I-dependent activation of the cell signaling pathways PI3K, Akt, and ERK1/2 and CDC25c. Blocking these pathways stops cancer cells from dividing and leads to cell death.”
Prof Jung Park continued, “Our study, showing that luteolin interferes with cell signaling in colon cancer cells, is a step forward in understanding how this flavonoid works. A fuller understanding of the in vivo results is essential to determine how it might be developed into an effective chemopreventive agent.”
Enriched skimmed milk may curb frequency of gout flare-ups
A daily dose of skimmed milk, enriched with 2 components found in dairy products, may help to curb the frequency of painful gout flare-ups, indicates research published online in the Annals of the Rheumatic Diseases
A daily dose of skimmed milk, enriched with two components found in dairy products, may help to curb the frequency of painful gout flare-ups, indicates research published online in the Annals of the Rheumatic Diseases.
Previous long term research has shown that the risk of gout is greater among those whose diet is low on dairy products.
And experimental studies indicate that certain components of dairy products, particularly glycomacropeptide (GMP) and G600 milk fat extract (G600), seem to dampen down the inflammatory response to gout crystals.
The authors studied the frequency of gout flare-ups in 120 patients with the condition over a period of three months. All the patients had experienced at least two flare-ups in the preceding four months.
The patients were divided into three different treatment groups: lactose powder; skimmed milk powder; or skimmed milk powder enriched with GMP and G600. Each powder was mixed in 250 ml of water as a vanilla flavoured shake and drunk daily.
The patients attended a rheumatology clinic monthly to check on their requirement for medication and their symptoms, which they recorded using a daily flare diary and validated pain scale.
There were no significant differences among the three groups at the start of the study in terms of frequency of gout flare-ups, pain, or drugs used to treat the condition.
In all, 102 patients completed the three month study. And the results showed that those on the enriched skimmed milk diet had a significantly greater reduction in gout flare-ups compared with the other two groups.
They also had greater improvements in pain and the amount of uric acid in their urine than those in the other two groups. This was matched by a trend towards a reduction in the number of tender joints.
The enriched skimmed milk diet did not boost weight gain or increase the levels of potentially harmful blood fats.
“This is the first reported randomised controlled trial of dietary intervention in gout management, and suggests that daily intake of skimmed milk powder enriched with GMP and G600 may reduce the frequency of gout flares,” conclude the authors.
Compounds in mate tea induce death in colon cancer cells
URBANA – Could preventing colon cancer be as simple as developing a taste for yerba mate tea? In a recent University of Illinois study, scientists showed that human colon cancer cells die when they are exposed to the approximate number of bioactive compounds present in one cup of this brew, which has long been consumed in South America for its medicinal properties.
“The caffeine derivatives in mate tea not only induced death in human colon cancer cells, they also reduced important markers of inflammation,” said Elvira de Mejia, a U of I associate professor of food chemistry and food toxicology.
That’s important because inflammation can trigger the steps of cancer progression, she said.
In the in vitro study, de Mejia and former graduate student Sirima Puangpraphant isolated, purified, and then treated human colon cancer cells with caffeoylquinic acid (CQA) derivatives from mate tea. As the scientists increased the CQA concentration, cancer cells died as a result of apoptosis.
“Put simply, the cancer cell self-destructs because its DNA has been damaged,” she said.
The ability to induce apoptosis, or cell death, is a promising tactic for therapeutic interventions in all types of cancer, she said.
de Mejia said they were able to identify the mechanism that led to cell death. Certain CQA derivatives dramatically decreased several markers of inflammation, including NF-kappa-B, which regulates many genes that affect the process through the production of important enzymes. Ultimately cancer cells died with the induction of two specific enzymes, caspase-3 and caspase-8, de Mejia said.
“If we can reduce the activity of NF-kappa-B, the important marker that links inflammation and cancer, we’ll be better able to control the transformation of normal cells to cancer cells,” she added.
The results of the study strongly suggest that the caffeine derivatives in mate tea have potential as anti-cancer agents and could also be helpful in other diseases associated with inflammation, she said.
But, because the colon and its microflora play a major role in the absorption and metabolism of caffeine-related compounds, the anti-inflammatory and anti-cancer effects of mate tea may be most useful in the colon.
“We believe there’s ample evidence to support drinking mate tea for its bioactive benefits, especially if you have reason to be concerned about colon cancer. Mate tea bags are available in health food stores and are increasingly available in large supermarkets,” she added.
The scientists have already completed and will soon publish the results of a study that compares the development of colon cancer in rats that drank mate tea as their only source of water with a control group that drank only water.
This in vitro study was published in Molecular Nutrition & Food Research, vol. 55, pp. 1509-1522, in 2011. Co-authors include Sirima Puangpraphant, now an assistant professor at Kasetsart University in Thailand; Greg Potts, an undergraduate student of the U of I; and Mark A. Berhow and Karl Vermillion of the USDA, ARS, National Center for Agricultural Utilization Research in Peoria, Illinois. The work was funded by the U of I Research Board and Puangpraphant’s Royal Thai Government Scholarship.
CU School of Medicine researchers look at effects of 2 common sweeteners on the body
AURORA, Colo. (Jan. 23, 2012) – With growing concern that excessive levels of fructose may pose a great health risk – causing high blood pressure, kidney disease and diabetes – researchers at the University of Colorado School of Medicine, along with their colleagues at the University of Florida, set out to see if two common sweeteners in western diets differ in their effects on the body in the first few hours after ingestion. The study, recently published in the journal Metabolism, took a closer look at high fructose corn syrup (HFCS) and table sugar (sucrose) and was led by Dr MyPhuong Le (now a postdoctoral fellow at the University of Colorado) and Dr Julie Johnson, a Professor of Pharmacogenomics at the University of Florida.
Both HFCS and sucrose have historically been considered to have nearly identical effects on the body. But this study finds that indeed there is a difference between the two.They found that the makeup of the sugars resulted in differences in how much fructose was absorbed into the circulation, and which could have potential impact on one’s health. Sucrose is 50 percent fructose and 50 percent glucose that is bonded together as a disaccharide (complex carbohydrate) and HFCS is a mixture of free fructose (55%) and free glucose (45%). It’s the difference in fructose amount that appears to create the ill health effects on the body.
Their study was conducted at the University of Florida, where they evaluated 40 men and women who were given 24 ounces of HFCS- or sugar-sweetened soft drinks. Careful measurements showed that the HFCS sweetened soft drinks resulted in significantly higher fructose levels than the sugar-sweetened drinks. Fructose is also known to increase uric acid levels that have been implicated in blood pressure, and the HFCS-sweetened drinks also resulted in a higher uric acid level and a 3 mm Hg greater rise in systolic blood pressure.
Dr Richard Johnson, a coauthor in the study and Chief of the Division of Renal Diseases and Hypertension at the University of Colorado, commented “Although both sweeteners are often considered the same in terms of their biological effects, this study demonstrates that there are subtle differences. Soft drinks containing HFCS result in slightly higher blood levels of fructose than sucrose-sweetened drinks, “said Johnson. “The next step is for new studies to address whether the long-term effects of these two sweeteners are different.”
More on legal remedies for ghostwriting
In an Essay that expands on a previous proposal to use the courts to prosecute those involved in ghostwriting on the basis of it being legal fraud, Xavier Bosch from the University of Barcelona, Spain and colleagues lay out three outline specific areas of legal liability in this week’s PLoS Medicine.
First, when an injured patient’s physician directly or indirectly relies upon a journal article containing false or manipulated safety and efficacy data, the authors (including “guest” authors), can be held legally liable for patient injuries, says the article. Second, guest authors of ghost-written articles published by Medicare- and Medicaid-recognized peer-reviewed medical journals used as clinical evidence for indications for off-label drugs articles may be liable under the federal False Claims Act for inducing the United States government to reimburse prescriptions under false pretenses. Finally, the authors argue, paying guest authors of ghostwritten papers—which may influence clinical judgment, increase product sales and government health care costs, and put patients at risk by misrepresenting risk-benefit— can mean that both physicians and sponsor companies may be liable under the federal Anti-Kickback Statute.
Although guest authors and pharmaceutical defendants may argue a First Amendment right to participate in ghostwriting, the authors say, the US Supreme Court has firmly held that the First Amendment does not shield fraud.
In the previous proposal, published in PLoS Medicine in August 2011, Simon Stern and Trudo Lemmens from the Faculties of Law and Medicine at the University of Toronto, Canada argued that it is irrelevant whether publications with academic guest authors are factually accurate. Rather, ghostwriting of medical journal articles raises serious ethical and legal concerns, bearing on the integrity of medical research and scientific evidence used in legal disputes. Furthermore, the false respectability afforded to claims of safety and effectiveness through the use of academic investigators risks undermining the integrity of biomedical research and patient care—an integrity that also underpins the use of scientific evidence in the courtroom.
According to these authors, medical journals, academic institutions, and professional disciplinary bodies have failed to enforce effective sanctions. Some journals, such as PLoS Medicine, have called for bans on future submissions by authors who act as guests, formal retraction if unacknowledged ghostwriting is discovered after publication, and reporting of authors’ misconduct to institutions. Although the authors agree that such actions may have an impact on academics concerned about their status and future publication options, they say that it is unclear whether journals can adequately monitor the practice.
They made the case for more effectively deterring the practice of ghostwriting through the imposition of legal liability on the ”guest authors” who lend their names to ghostwritten articles. The authors say: “We argue that a guest author’s claim for credit of an article written by someone else constitutes legal fraud, and may give rise to claims that could be pursued in a class action based on the Racketeer Influenced and Corrupt Organizations Act [RICO].”
The authors said: “The same fraud could support claims of ”fraud on the court” against a pharmaceutical company that has used ghostwritten articles in litigation. This claim also appropriately reflects the negative impact of ghostwriting on the legal system.”
Ralph’s Note: YES YES YES!!!!
Study examines link between vaccinations and exposure to compound widely used in food packaging
CHICAGO – Elevated exposures in children to perfluorinated compounds, which are widely used in manufacturing and food packaging, were associated with lower antibody responses to routine childhood immunizations, according to a study in the January 25 issue of JAMA.
“Fluorine-substituted organic compounds have thousands of important industrial and manufacturing applications and occur widely in surfactants and repellants in food packaging and textile impregnation. The perfluorinated compounds (PFCs) are highly persistent and cause contamination of drinking water, food, and food chains,” according to background information in the article. The most common PFCs, perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS), are commonly detected in human serum. The immune system in mice has recently been shown to be highly sensitive to PFOS, with adverse effects on humoral (pertaining to elements in the blood or other body fluids) immunity detected at blood concentrations similar to those occurring in the U.S. population, but adverse health effects of PFC exposure are poorly understood.
Philippe Grandjean, M.D., D.M.Sc., of the Harvard School of Public Health, Boston, and colleagues conducted an investigation of antibody responses to diphtheria and tetanus toxoids as indicators of immunotoxicity in children, choosing the fishing community of the Faroe Islands, where frequent intake of marine food is associated with increased exposures to PFCs. The Faroe Islands are a country in the Norwegian Sea located between Scotland and Iceland. The study included 656 children born at the National Hospital in the Faroe Islands during 1999-2001. Follow-up was through 2008, with 587 participants. The researchers measured serum antibody concentrations against tetanus and diphtheria toxoids at ages 5 and 7 years of the children.
Similar to results of prior studies in the United States, the PFCs with the highest serum concentrations were PFOS and PFOA. Multiple analyses showed that prenatal exposures to both PFOS and PFOA, as indicated by the maternal serum concentrations, were negatively associated with antidiphtheria antibody concentrations, with a 2-fold increase in PFOS exposure associated with a difference in antibody concentration of -39 percent at age 5 years before the booster. All but 1 of the PFC concentrations measured in the child’s serum at age 5 years showed negative associations with the antibody concentrations measured in serum both before and after the booster. For antibody concentrations at age 7 years, all PFC exposures measured at age 5 years showed negative associations, most strongly for PFOA and PFOS, with a 2-fold increase in PFOA exposure associated with differences of -36 percent and -25 percent for tetanus and diphtheria, respectively.
At a doubled postnatal PFC exposure, the overall antibody concentration at age 7 years was approximately halved. This significant difference remained after adjustment for prenatal PFC exposure. A 2-fold increase in PFOS and PFOA concentrations at age 5 years was associated with an approximately 2.4 and 4.2 higher odds of falling below a clinically protective level of 0.1 IU/ml for tetanus and diphtheria antibodies, respectively, at age 7 years.
“If the associations are causal, the clinical importance of our findings is therefore that PFC exposure may increase a child’s risk for not being protected against diphtheria and tetanus, despite a full schedule of vaccinations. Adequate formation of specific antibodies relies on several important immune functions, and serum antibody concentrations triggered by standardized antigen stimulations may therefore reflect the more general efficacy of the immune system in relation to infection. For this reason, PFC-associated decreases in antibody concentrations may indicate the potential existence of immune system deficits beyond the protection against the 2 specific bacteria examined in this study,” the authors write.
“These findings suggest a decreased effect of childhood vaccines and may reflect a more general immune system deficit. Assessment of risk related to exposure to these contaminants therefore needs to consider the immunotoxic potential of the PFCs.”
Cocoa could prevent intestinal pathologies such as colon cancer
IMAGE:Cocoa is an excellent source of phytochemical compounds that have potential health benefits.
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A new study on living animals has shown for the first time that eating cocoa (the raw material in chocolate) can help to prevent intestinal complaints linked to oxidative stress, including colon carcinogenesis onset caused by chemical substances.
The growing interest amongst the scientific community to identify those foods capable of preventing diseases has now categorized cocoa as a ‘superfood’. It has been recognised as an excellent source of phytochemical compounds, which offer potential health benefits.
Headed by scientists from the Institute of Food Science and Technology and Nutrition (ICTAN) and recently published in the Molecular Nutrition & Food Research journal, the new study supports this idea and upholds that cacao consumption helps to prevent intestinal complaints linked to oxidative stress, such as the onset of chemically induced colon carcinogenesis.
“Being exposed to different poisons in the diet like toxins, mutagens and procarcinogens, the intestinal mucus is very susceptible to pathologies,” explains María Ángeles Martín Arribas, lead author of the study and researcher at ICTAN. She adds that “foods like cocoa, which is rich in polyphenols, seems to play an important role in protecting against disease.”
The study on live animals (rats) has for the first time confirmed the potential protection effect that flavonoids in cocoa have against colon cancer onset. For eight weeks the authors of the study fed the rats with a cocoa-rich (12%) diet and carcinogenesis was induced.
Doctor Martín Arribas outlines that “four weeks after being administered with the chemical compound azoxymethane (AOM), intestinal mucus from premalignant neoplastic lesions appeared. These lesions are called ‘aberrant crypt foci’ and are considered to be good markers of colon cancer pathogenesis.”
IMAGE:A cocoa-rich diet prevents the formation of aberrant crypt foci in the colon (marked with an arrow) induced by pro-carcinogen azoxymethane.
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The results of the study showed that the rats fed a cocoa-rich diet had a significantly reduced number of aberrant crypts in the colon induced by the carcinogen. Likewise, this sample saw an improvement in their endogenous antioxidant defences and a decrease in the markers of oxidative damage induced by the toxic compound in this cell.
The researchers conclude that the protection effect of cocoa can stop cell-signalling pathways involved in cell proliferation and, therefore, subsequent neoplasty and tumour formation. Lastly, the animals fed with the cocoa-rich diet showed an increase in apoptosis or programmed cell death as a chemoprevention mechanism against the development of the carcinogenesis.
Although more research is required to determine what bioactive compounds in cocoa are responsible for such effects, the authors conclude that a cocoa-rich diet seems capable of reducing induced oxidative stress. It could also have protection properties in the initial stages of colon cancer as it reduces premalignant neoplastic lesion formation.
A not-so-guilty pleasure
Cocoa is one of the ingredients in chocolate. It is one of the richest foods in phenolic compounds, mainly in flavonoids like procyanidins, catechins and epicatechins, which have numerous beneficial biological activities in the prevention of cardiovascular diseases and cancer (mainly colorectal cancer).
In fact, compared to other foods with a high flavonoid content, cocoa has a high level of procyanidins with limited bioavailability. These flavonoids are therefore found in their highest concentrations in the intestine where they neutralise many oxidants.
High fructose consumption by adolescents may put them at cardiovascular risk
Evidence of cardiovascular disease and diabetes risk is present in the blood of adolescents who consume a lot of fructose, a scenario that worsens in the face of excess belly fat, researchers report.
An analysis of 559 adolescents age 14-18 correlated high-fructose diets with higher blood pressure, fasting glucose, insulin resistance and inflammatory factors that contribute to heart and vascular disease.
Heavy consumers of the mega-sweetener also tend to have lower levels of cardiovascular protectors such as such as HDL cholesterol and adiponectin, according to researchers at the Medical College of Georgia at Georgia Health Sciences University.
These dangerous trends are exacerbated by fat around their midsection, called visceral adiposity, another known risk factor for cardiovascular disease and diabetes. The association did not hold up for adolescents with more generalized, subcutaneous fat.
“It is so very important to provide a healthy balance of high-quality food to our children and to really pay close attention to the fructose and sucrose they are consuming at their home or anyone else’s,” said Dr. Vanessa Bundy, an MCG pediatric resident. Drs. Bundy and Norman Pollock, bone biologist at MCG’s Georgia Prevention Institute are co-first authors on the study published in The Journal of Nutrition.
“The nutrition that caregivers provide their children will either contribute to their overall health and development or potentially contribute to cardiovascular disease at an early age,” Bundy said. The best way caregivers can support healthy nutrition is to be good role models, she said. A healthy diet with plenty of physical activity – not dieting – is the best prescription for growing children.
“Adolescents consume the most fructose so it’s really important to not only measure the levels of fructose but to look at what it might be doing to their bodies currently and, hopefully, to look at cardiovascular disease outcomes as they grow,” Pollock said.
While animal studies have had similar findings, evidence in children is needed to support dramatic steps to curb consumption, such as asking schools to remove soda and other vending machines or, at least, to limit access, Pollock said. The researchers noted that more study is needed to flesh out the relationship between high fructose consumption and cardiovascular risk and whether these early associations forebode adult disease.
Fructose, or fruit sugar, is found in fruits and veggies but also in high fructose corn syrup, the sweetener used liberally in processed foods and beverages. Researchers suspect growing bodies crave the cheap, strong sweetener and companies often target young consumers in ads.
“Fructose itself is metabolized differently than other sugars and has some byproducts that are believed to be bad for us,” Bundy said. “The overall amount of fructose that is in high fructose corn syrup is not much different than the amount in table sugar but it’s believed there’s something in the syrup processing that plays a role in the bad byproducts of metabolism.”
The study took a “snapshot” of the adolescents’ lives, looking at overall fructose consumption, general diet history and body fat.
“A unique aspect of our study design is that we took into account the fructose released from sucrose during digestion along with the fructose found in foods and beverages,” Pollock said. “Because sucrose is broken down into fructose and glucose before it arrives at the liver for metabolism, it is important to consider the additional fructose from sucrose when determining the overall health effect of fructose.”
‘DIMming’ cancer growth — STAT: Diindolylmethane suppresses ovarian cancer
Ovarian cancer is a major cause of death worldwide. Approximately 25,000 women will be diagnosed with ovarian cancer this year and 15,000 women will die from it in the United States alone. The novel anti-cancer drug diindolylmethane (DIM) has been shown in laboratory to inhibit the growth of ovarian cancer cells. New research published in BioMed Central’s open access journal BMC Medicine has looked in detail at the action of DIM and showed that it works by blocking the activation and production of the transcription factor STAT3. DIM also enhances the anti-cancer effect of the platinum-based chemotherapy drug cisplatin.
Scientists from Texas Tech University Health Sciences Center, Amarillo already knew that DIM inhibited the growth of ovarian cancer cells but have now found that DIM causes ovarian cancer cell death (apoptosis). Not only was DIM able to kill cells but it also prevented cell invasion and angiogenesis, both of which are necessary for a cancer to grow.
STAT transcription factors are involved in the growth and survival of cells and are switched on by growth factors and immune system messengers (cytokines) such as IL-6. STAT3 is activated in 90% of ovarian cancers, however DIM was able to inhibit activation of STAT3 by preventing phosphorylation in response to IL-6. In a double whammy DIM also reduced the amount of IL-6 and the growth factor involved in angiogenesis (VEGF) in ovarian cancer cells.
Women with ovarian cancer are often treated with platinum containing chemotherapy drugs. However patients treated with cisplatin often relapse or fail to respond and cisplatin resistance is known to be associated with an increase in STAT3. In this study the combination of cisplatin and DIM suppressed tumour growth in mice by an extra 50% compared to cisplatin alone.
Prof Sanjay K. Srivastava and Prabodh K. Kandala who performed the research explained, “DIM increases the effect of cisplatin, without being toxic to normal ovarian cells, by targeting STAT3 signaling and increasing apoptosis. Cisplatin is very toxic and has severe side effects. If co-treatment with DIM means that a low dose of cisplatin can be given to patients without the loss of therapeutic effect, but with reduced side effects, it would represent a significant breakthrough in clinical practice.”
Pycnogenol (French maritime pine bark extract) shown to improve visible signs of aging in new study
Natural supplement found to improve skin elasticity by 25 percent and skin hydration by 8 percent
(Jan. 25, 2012) – HOBOKEN, NJ – Human skin is the body’s first line of defense and often mirrors the health, nutritional status and age of a person. Over time, skin shows signs of aging due to the gradual breakdown of collagen and elastin. However, skin can be rebuilt and made healthier no matter one’s age. Natural supplement Pycnogenol® (pic-noj-en-all), an antioxidant plant extract from the bark of the French maritime pine tree, was found to improve skin hydration and elasticity in women in a clinical trial published this month in Skin Pharmacology and Physiology.
The study was conducted at the Leibniz Research Institute for Environmental Medicine (IUF) in Dusseldorf, Germany and examined 20 healthy women, aged 55 – 68 years. Participants were given 75 mg of Pycnogenol® per day, over a period of 12 weeks. Skin hydration, skin elasticity and skin fatigue were assessed by non-invasive biophysical methods at trial start and after six and 12 weeks. In addition, at the beginning and again after 12 weeks of Pycnogenol® supplementation, each time, a biopsy was obtained to assess gene expression of HAS-1 and COL1A1 and COL1A2. The study found that:
Pycnogenol® elevated COL1A1 by 29 percent and COL1A2 by 41 percent and increased hyaluronic acid production in skin by 44 percent
Pycnogenol® enhanced skin elasticity by 25 percent, in addition to skin hydration by eight percent, and was especially noticeable in women who had dry skin from the start, with an increase of 21 percent
Pycnogenol® decreased skin fatigue considerably
Pycnogenol® reduced skin wrinkles by three percent and increased skin smoothness by six percent
“To date, Pycnogenol® is the only natural supplement that stimulates hyaluronic acid production in human skin. And, we are encouraged by the molecular evidence confirmed in this study that shows nutritional supplementation with Pycnogenol® benefits human skin,” explains Dr. Jean Krutmann, the lead researcher from the Leibniz Research Institute in Dusseldorf, Germany.
Study results confirmed Pycnogenol® improved skin at a physiological and molecular level. Pycnogenol® increased hyaluronic acid in women by 44 percent after 12 weeks of supplementation. Hyaluronic acid binds large quantities of water in the skin and in other tissues, such as cartilage. An increased amount of hyaluronic acid explains the increased skin hydration, higher elasticity and overall smoother skin appearance found in women taking Pycnogenol®.
“This exciting and technically advanced investigation with women representing actual consumer profiles greatly supports our efforts for targeting the skin beauty category for both dietary supplements and functional foods,” says Victor Ferrari, CEO of Horphag Research, exclusive worldwide suppliers of Pycnogenol®, who welcomes the publication.
According to Ferrari, beauty from within has been a driver in Horphag’s business for the last several years, with Asian markets providing numerous Pycnogenol® products in the skincare field. This study joins a sizable and largely expanding portfolio of already established skin research on Pycnogenol®. It confirms previous indications that Pycnogenol® improves human skin conditions, including promoting glowing skin and reducing the appearance of over-pigmentation and skin inflammation, resulting in a more even complexion.
Avastin, Sutent increase breast cancer stem cells, U-M study shows
Finding could explain limited success of anti-angiogenesis treatments in breast cancer
Ann Arbor – Cancer treatments designed to block the growth of blood vessels were found to increase the number of cancer stem cells in breast tumors in mice, suggesting a possible explanation for why these drugs don’t lead to longer survival, according to a new study by researchers at the University of Michigan Comprehensive Cancer Center.
Meet the Expert:Max Wicha, M.D. Learn more: Breast cancer information Stem Cells in Breast Cancer information Read the abstract
The drugs Avastin and Sutent have been looked at as potential breast cancer treatments. But while they do shrink tumors and slow the time till the cancer progresses, the effect does not last, and the cancer eventually regrows and spreads.
“This study provides an explanation for the clinical trial results demonstrating that in women with breast cancer antiangiogenic agents such as Avastin delay the time to tumor recurrence but do not affect patient survival. If our results apply to the clinic, it suggests that in order to be effective, these agents will need to be combined with cancer stem cell inhibitors, an approach now being explored in the laboratory,” says study author Max S. Wicha, M.D., director of the U-M Comprehensive Cancer Center.
The researchers treated mice with breast cancer using Avastin (bevacizumab) and Sutent (sunitinib), both of which work by stopping the growth and formation of blood vessels, a process called angiogenesis. The researchers found that tumors treated with these drugs developed more cancer stem cells, the small number of cells within a tumor that fuel a cancer’s growth and spread and that are often resistant to standard treatment. Both the number of cancer stem cells and the percentage of cancer stem cells that make up the tumor increased after being treated with each of these therapies.
The researchers found that the cancer stem cells increased because of a cellular response to low oxygen, a condition called hypoxia. And they were able to determine the specific pathways involved in hypoxia that activate the cancer stem cells.
Results of the study appear online in the Proceedings of the National Academy of Sciences Early Edition.
The U.S. Food and Drug Administration recently revoked approval of Avastin for treating breast cancer, although the drug is approved for use in other types of cancer. The reversal was in response to clinical trials showing that the drug’s benefit was short-lived, with breast cancer patients quickly relapsing and the cancer becoming more invasive and spreading further throughout the body. Overall, the drug did not help patients live any longer.
The current study suggests the possibility of combining anti-angiogenesis drugs with a cancer stem cell inhibitor to enhance the benefit of this treatment. The researchers are testing this approach in mice and preliminary data looks promising.
IBD travelers are not at higher risk of contracting intestinal infections
‘When traveling in the tropics, my IBD felt the best ever,’ recall patients
Inflammatory bowel disease (IBD) travelers have an increased risk of illness during trips to industrialized countries, but not to developing or tropical regions, according to a new study in Clinical Gastroenterology and Hepatology, the official journal of the American Gastroenterological Association.
“Inflammatory bowel disease patients are often advised to avoid travel, especially to the developing world. However, we found that the absolute risk of illness is small and most episodes were mild,” said Shomron Ben-Horin, MD, of the Sheba Medical Center in Tel Hashomer, Israel and lead author of this study. “If an inflammatory bowel disease patient has been in remission for at least three months, I recommend they take their dream vacation.”
In this study, doctors studied 222 IBD patients and 224 healthy individuals (controls) during 1,099 total trips. They collected data via structured questionnaires, personal interviews and chart reviews. While traveling to industrialized countries, illness occurred during 13.9 percent of the trips made by IBD patients in contrast to 3.3 percent of trips made by controls. However, during travel to developing or tropical regions, the rate of illness was similar between both groups: 17 percent for IBD patients versus 21 percent for controls. Because traveler diarrhea and other intestinal infectious diseases predominately afflict travelers to developing countries, this unexpected observation suggests that IBD travelers as a whole do not stand a higher risk of contracting intestinal infections while traveling compared with the non-IBD population. Interestingly, IBD patients who had set out to travel after enjoying more than three months without symptomatic disease (a state termed as clinical remission) had an overall similar risk of illness during the trip as their healthy counterparts, regardless of the country destinations.
IBD is a chronic and often debilitating intestinal disorder, which adversely affects quality of life, including concern over safety issues in relation to traveling abroad. In the absence of enough data on the risks of traveling among IBD patients, many physicians advise IBD patients against traveling, especially to developing regions of the world. Insurance companies are often reluctant to insure IBD travelers, a refusal that is hard to rebut in the absence of data.
Taken together, these restrictions on traveling severely impede the overall quality of life of IBD patients. Until now, it was unclear whether this significant toll was based on a genuine increase in health risk during traveling in IBD patients. Results from this study indicate a comparable safety of travelling in the tropics for IBD patients and healthy individuals. The results also suggest that traveling while in clinical remission of at least three months should be strongly advocated, as it significantly reduces the risk for illness during traveling. However, the investigators stress that travelers to developing and tropic regions of the world are still at risk of several vaccine-preventable infections and should always consult a travel clinic before the trip and get the appropriate vaccinations.
New standard for vitamin D testing to ensure accurate test results
At a time of increasing concern about low vitamin D levels in the world’s population and increased use of blood tests for the vitamin, scientists are reporting development of a much-needed reference material to assure that measurements of vitamin D levels are accurate. The report appears in ACS’ journal Analytical Chemistry.
Karen Phinney and colleagues explain that medical research suggests vitamin D deficiency or insufficiency may be even more common than previously thought and a risk factor for more than just bone diseases. An estimated 50-75 percent of people in the U.S. may not have enough vitamin D in their bodies. Low levels of vitamin D have been linked to the development of several conditions, including rickets (soft and deformed bones), osteoporosis, some cancers, multiple sclerosis and Parkinson’s disease. People can make their own vitamin D simply by rolling up their shirt sleeves and exposing their skin to sunlight. But for those cooped up in offices all day long, food and dietary supplements also can provide vitamin D. With this renewed interest in vitamin D, scientists need an accurate way to measure its levels in the blood. Measuring vitamin D itself doesn’t work because it is rapidly changed into another form in the liver. That’s why current methods detect levels of a vitamin D metabolite called 25(OH)D. However, the test methods don’t always agree and produce different results. To help laboratories come up with consistent and accurate methods, the researchers developed a Standard Reference Material called SRM 972, the first certified reference material for the determination of the metabolite in human serum (a component of blood).
The researchers developed four versions of the standard, with different levels of the vitamin D metabolites 25(OH)D2 and 25(OH)D3 in human serum. They also determined the levels of 3-epi-25(OH)D in the adult human serum samples. Surprisingly, they found that this metabolite — previously thought to only exist in the blood of infants — was present in adult serum. “This reference material provides a mechanism to ensure measurement accuracy and comparability and represents a first step toward standardization of 25(OH)D measurements,” say the researchers.
High animal fat diet increases gestational diabetes risk
NIH study shows animal fat before conception linked to pregnancy related condition
Women who consumed a diet high in animal fat and cholesterol before pregnancy were at higher risk for gestational diabetes than women whose diets were lower in animal fat and cholesterol, according to researchers at the National Institutes of Health and Harvard University.
Gestational diabetes is a form of diabetes seen during pregnancy. Gestational diabetes increases the risk for certain pregnancy complications and health problems in the newborn.
Women whose diets were high in total fat or other kinds of fats—but not in animal fat or cholesterol—did not have an increased risk.
Moreover, the increased risk for gestational diabetes seen with animal fat and cholesterol appeared to be independent of other, dietary and non-dietary, risk factors for gestational diabetes. For example, exercise is known to reduce the risk of gestational diabetes. Among women who exercised, however, those who consumed higher amounts of animal fat and cholesterol had a higher risk than those whose diets were lower in these types of fat.
“Our findings indicate that women who reduce the proportion of animal fat and cholesterol in their diets before pregnancy may lower their risk for gestational diabetes during pregnancy,” said senior author Cuilin Zhang, M.D., M.P.H., Ph.D., of the Epidemiology Branch at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), one of three NIH institutes supporting the study.
The researchers concluded that changing the source of 5 percent of dietary calories from animal fat to plant-derived sources could decrease a woman’s risk for gestational diabetes by 7 percent.
The U.S. Department of Agriculture website, ChooseMyPlate.gov, contains information on healthy eating for children and adults, as well as health and nutrition information for pregnant and breast feeding women.
First author Katherine Bowers, Ph.D., conducted the research with NICHD colleagues Dr. Zhang and Edwina Yeung, Ph.D., and with Deirdre K. Tobias and Frank B. Hu, M.D., M.P.H., Ph.D., of Harvard University, in Boston.
Their findings appear online in the American Journal of Clinical Nutrition.
The research was also funded by the National Cancer Institute and the National Institute of Diabetes and Digestive and Kidney Diseases.
The researchers utilized information from more than 13,000 women participating in the Nurses’ Health Study II. The women were 22 to 45 years old when they enrolled in the study. Every two years they responded to questions on their general health, pregnancy status, and lifestyle habits, such as consuming alcohol or smoking. In addition, every four years they completed a comprehensive survey about the kinds of food and drink they consumed.
About 6 percent of the participants reported having been diagnosed with gestational diabetes. The researchers calculated the amount of animal fat in participants’ diets as a percentage of total calories and divided participants into five groups, or quintiles, based on those percentages. Then the researchers compared the risk for developing gestational diabetes for each group. Women in the highest quintile of intake had almost double the risk for gestational diabetes compared to women in the lowest quintile.
They also observed that women in the highest quintile for cholesterol consumption were 45 percent more likely to develop gestational diabetes than were women in the lowest quintile.
“This is the largest study to date of the effects of a pre-pregnancy diet on gestational diabetes,” Dr. Bowers said. “Additional research may lead to increased understanding of how a mother’s diet before and during pregnancy influences her metabolism during pregnancy, which may have important implications for the baby’s health at birth and later in life.”
Newly engineered highly transmissible H5N1 strain ignites controversy about balancing scientific discovery and public safety
Annals of Internal Medicine early release
Philadelphia — Scientists have engineered a new strain of H5N1 (commonly known as bird flu) to be readily transmitted between humans. Two perspectives being published early online in Annals of Internal Medicine (www.annals.org), the flagship journal of the American College of Physicians, raise concerns about if and how this research should be continued, and how the data should be shared for the benefit of public health.
The currently circulating H5N1 virus has an extremely high case-fatality rate, killing about 60 percent of the over 500 confirmed human cases. However, unlike seasonal flu, to date H5N1 has not easily spread between humans. Recently, two scientific teams (not associated with the Annals perspectives authors) engineered the H5N1 virus to make it readily transmissible between ferrets. This means that it may be able to make it easily transmissible between humans as well. Controversy has emerged about the safety and appropriateness of this research.
The National Science Advisory Board for Biosecurity (NSABB) has recommended that the H5N1 research be published, but with significant redactions. Specifically, journals should publish the work without detailed methodology, to reduce the risk of replication and purposeful misuse. This recommendation has divided the scientific community into those who are for censorship, and those who oppose it.
In the first Annals perspective, Thomas V. Inglesby, MD, CEO and Director of the Center for Biosecurity of University of Pittsburgh Medical Center, writes that the potential consequences of an engineered human transmissible H5N1 strain are stunning. If the newly engineered strain were to escape the laboratory and spread as widely as seasonal flu, it could endanger the lives of hundreds of millions of persons.
Whether the virus escapes the lab by accident or on purpose, the highly contagious and deadly nature of the mutant strain could result in catastrophe. The work was done to increase scientific knowledge of H5N1. But there is no scientific evidence that a strain like the one developed in the laboratory will ever occur naturally. Dr. Inglesby suggests that the harms of the research therefore outweigh the benefits.
“If we are asking society to take the substantial and unprecedented risks associated with a human-transmissible H5N1 strain with a nearly 60 percent case-fatality rate, we had better have a compelling, concrete, and realistic public health justification for it,” Dr. Inglesby writes. If experimentation must continue, he recommends very restricted use, like the approach that has been taken with smallpox.
Andrew T. Pavia, MD, Chief of the Division of Pediatric Infectious Diseases at the University of Utah Health Sciences Center and Primary Children’s Hospital, authored the second Annals perspective on the topic.
Dr. Pavia, argues that the H5N1 virus may not be as easy to transmit between humans as some speculate. With regard for the use of H5N1 as a bioweapon, Dr. Pavia suggests that the scenario may be unlikely. To manipulate H5N1 as a weapon, the terrorist would need substantial scientific skill and knowledge of precise methods used in the studies.
He writes that with proper safeguards, these and future studies should proceed and can increase critical scientific understanding of influenza. Currently, there is not a transparent and thoughtful mechanism to ensure the provision of details only to those with a legitimate need for the data and to decide who those people are. Dr. Pavia thus generally agrees with the approach taken by the NSABB and argues creating more dangerous pathogens in a laboratory has its purpose. According to Dr. Pavia, “We must have a careful and balanced approach that is neither too timid in permitting the performance and sharing of critical research nor too naive in confronting the biosecurity issues posed by that research.”
Meanwhile the investigators themselves have announced a 60 day self-mortorium on their research while debate continues.
NIH study shows caffeine consumption linked to estrogen changes
Moderate caffeine intake associated with higher level for Asians, lower for whites
Asian women who consumed an average of 200 milligrams or more of caffeine a day—the equivalent of roughly two cups of coffee—had elevated estrogen levels when compared to women who consumed less, according to a study of reproductive age women by researchers at the National Institutes of Health and other institutions.
However, white women who consumed 200 milligrams or more of caffeine a day had slightly lower estrogen levels than women who consumed less. Black women who consumed 200 milligrams or more of caffeine a day were found to have elevated estrogen levels, but this result was not statistically significant.
Total caffeine intake was calculated from any of the following sources: coffee, black tea, green tea, and caffeinated soda.
Findings differed slightly when the source of caffeine was considered singly. Consuming 200 milligrams or more of caffeine from coffee mirrored the findings for overall caffeine consumption, with Asians having elevated estrogen levels, whites having lower estrogen levels, and the results for blacks not statistically significant. However, consumption of more than one cup each day of caffeinated soda or green tea was associated with a higher estrogen level in Asians, whites, and blacks.
The changes in estrogen levels among the women who took part in the study did not appear to affect ovulation. Studies conducted in animals had suggested that caffeine might interfere with ovulation.
The study was published online in the American Journal of Clinical Nutrition.
“The results indicate that caffeine consumption among women of child-bearing age influences estrogen levels,” said Enrique Schisterman, Ph.D., of the Division of Epidemiology, Statistics and Prevention Research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the NIH institute where some of the research was conducted. “Short term, these variations in estrogen levels among different groups do not appear to have any pronounced effects. We know that variations in estrogen level are associated with such disorders as endometriosis, osteoporosis, and endometrial, breast, and ovarian cancers. Because long term caffeine consumption has the potential to influence estrogen levels over a long period of time, it makes sense to take caffeine consumption into account when designing studies to understand these disorders.”
The study authors noted that 89 percent of U.S. women from 18-34 years of age consume the caffeine equivalent of 1.5 to two cups of coffee a day.
The study’s first author was Karen C. Schliep, Ph. D., M.S.P.H., from the University of Utah, Salt Lake City, who conducted the study during a research appointment at NICHD. Dr. Schliep undertook the research with Dr. Schisterman and colleagues at the University of Utah, the NICHD and the State University of New York at Buffalo.
More than 250 women from 18 to 44 years old participated in the study between 2005 and 2007. On average, they consumed 90 milligrams of caffeine a day, approximately equivalent to one cup of caffeinated coffee.
Most of the participants in the study reported to the study clinic one to three times a week for two menstrual cycles. Their visits were scheduled to correspond with specific stages of the menstrual cycle. At the visits, the women reported what they had eaten in the last 24 hours and answered questions about their exercise, sleep, smoking and other aspects of their lifestyle and reproductive hormone levels were measured in blood. The study authors noted that collection of these details during multiple time points across two menstrual cycles produced more precise information about the link between caffeine and hormones than was possible in earlier studies. The researchers also noted that the study participants were more racially diverse than those who took part in previous studies.
Grape seed extract kills head and neck cancer cells, leaves healthy cells unharmed
January 26, 2012 By Garth SundemLeave a Comment
Grape seed extract kills head and neck squamous cell carcinoma cells while leaving healthy cells unharmed (image courtesy of Flickr user Anders Ljungberg)
Nearly 12,000 people will die of head and neck cancer in the United States this year and worldwide cases will exceed half a million.
A study published this week in the journal Carcinogenesis shows that in both cell lines and mouse models, grape seed extract (GSE) kills head and neck squamous cell carcinoma cells, while leaving healthy cells unharmed.
“It’s a rather dramatic effect,” says Rajesh Agarwal, PhD, investigator at the University of Colorado Cancer Center and professor at the Skaggs School of Pharmaceutical Sciences.
It depends in large part, says Agarwal, on a healthy cell’s ability to wait out damage.
“Cancer cells are fast-growing cells,” Agarwal says. “Not only that, but they are necessarily fast growing. When conditions exist in which they can’t grow, they die.”
Grape seed extract creates these conditions that are unfavorable to growth. Specifically, the paper shows that grape seed extract both damages cancer cells’ DNA (via increased reactive oxygen species) and stops the pathways that allow repair (as seen by decreased levels of the DNA repair molecules Brca1 and Rad51 and DNA repair foci).
“Yet we saw absolutely no toxicity to the mice, themselves,” Agarwal says.
Rajesh Agarwal, PhD, investigator at the University of Colorado Cancer Center and professor at the Skaggs School of Pharmaceutical Sciences
Again, the grape seed extract killed the cancer cells but not the healthy cells.
“I think the whole point is that cancer cells have a lot of defective pathways and they are very vulnerable if you target those pathways. The same is not true of healthy cells,” Agarwal says.
The Agarwal Lab hopes to move in the direction of clinical trials of grape seed extract, potentially as an addition to second-line therapies that target head and neck squamous cell carcinoma that has failed a first treatment.
This work was supported by the R01 grants AT003623 from the National Center for Complementary and Alternative Medicine and CA91883 from the National Cancer Institute, NIH.
Bedwetting can be due to undiagnosed constipation, research shows
Winston-Salem, N.C. – Jan. 27, 2012 – Bedwetting isn’t always due to problems with the bladder, according to new research by Wake Forest Baptist Medical Center. Constipation is often the culprit; and if it isn’t diagnosed, children and their parents must endure an unnecessarily long, costly and difficult quest to cure nighttime wetting.
Reporting online in the journal Urology, researchers found that 30 children and adolescents who sought treatment for bedwetting all had large amounts of stool in their rectums, despite the majority having normal bowel habits. After treatment with laxative therapy, 25 of the children (83 percent) were cured of bedwetting within three months.
“Having too much stool in the rectum reduces bladder capacity,” said lead author Steve J. Hodges, M.D., assistant professor of urology at Wake Forest Baptist. “Our study showed that a large percentage of these children were cured of nighttime wetting after laxative therapy. Parents try all sorts of things to treat bedwetting — from alarms to restricting liquids. In many children, the reason they don’t work is that constipation is the problem.”
Hodges said the link between bedwetting and excess stool in the rectum, which is the lower five to six inches of the intestine, was first reported in 1986. However, he said the finding did not lead to a dramatic change in clinical practice, perhaps because the definition of constipation is not standardized or uniformly understood by all physicians and lay people.
“The definition for constipation is confusing and children and their parents often aren’t aware the child is constipated,” said Hodges. “In our study, X-rays revealed that all the children had excess stool in their rectums that could interfere with normal bladder function. However, only three of the children described bowel habits consistent with constipation.”
Hodges explained that guidelines of the International Children’s Continence Society recommend asking children and their parents if the child’s bowel movements occur irregularly (less often than every other day) and if the stool consistency is hard.
“These questions focus on functional constipation and cannot help identify children with rectums that are enlarged and interfering with bladder capacity,” said Hodges. “The kind of constipation associated with bedwetting occurs when children put off going to the bathroom. This causes stool to back up and their bowels to never be fully emptied. We believe that treating this condition can cure bedwetting.”
Children in the study ranged from 5 to 15 years old. The constipated children were treated with an initial bowel cleanout using polyethylene glycol (Miralax®), which softens the stools by causing them to retain water. In children whose rectums remained enlarged after this therapy, enemas or stimulant laxatives were used.
Hodges cautioned that any medical therapy for bedwetting should be overseen by a physician.
The study used abdominal X-rays to identify the children with excess stool in their rectums. Hodges and radiologists at Wake Forest Baptist developed a special diagnostic method that involves measuring rectal size on the X-ray. He said rectal ultrasound could also be used for diagnosis.
“The importance of diagnosing this condition cannot be overstated,” Hodges said. “When it is missed, children may be subjected to unnecessary surgery and the side effects of medications. We challenge physicians considering medications or surgery as a treatment for bedwetting to obtain an X-ray or ultrasound first.”
The study involved reviewing the charts of 30 consecutive patients treated for bedwetting. The authors cautioned that some cases may have improved on their own over time. They said a more accurate measure of the treatment’s success would be to randomly assign constipated children to laxative therapy or an inactive therapy, an approach that would identify true response from cases that would resolve over time.
Hodges’ co-author on the research is Evelyn Y. Anthony, MD, a radiologist at Wake Forest Baptist.
Hodges has written a book for consumers that covers this and other pediatric urology issues. “It’s No Accident: Breakthrough Solutions To Your Child’s Wetting, Constipation, UTIs, and Other Potty Problems,” published by Globe Pequot Press, will be released in early February.
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