CNO Report 181
Release Date 17 MAY 2014
Draft Report Compiled by
In this Issue:
- Study finds large increase in type 1 and 2 diabetes among US youth
- Compound Formula Rehmannia alleviates dyskinesia in Parkinson’s disease
- Low testosterone levels may indicate worsening of disease for men with prostate cancer
- New cause of high blood pressure and heart disease discovered
- Hypertension related to new cancer therapies — a new syndrome emerges
- Novel antioxidant makes old arteries seem young again, CU-Boulder study finds
- Eating more fruits, vegetables may cut stroke risk worldwide
- Gluten-free diet reduces risk of type 1 diabetes in mice
- Low-carbohydrate diet reduced inflammation
- Calcium supplements not associated with increased risk of cardiovascular disease in women
- Fourfold increase in the rate of diagnosed cases of celiac disease in the UK
- Understanding aspirin’s effect on wound healing offers hope for treating chronic wounds
- Brain may never fully recover from exposure to paint, glue, degreasers
- Smart drugs pose special risks to the developing brain of young people
- Forgiving a Wrong May Actually Make It Easier to Forget
- PCB increases harmful effects of smoking
- Zinc supplementation boosts immune system in children, Cochrane Review finds
- Sugar implicated in cardiovascular disease risk independent of weight gain
- ‘Bystander’ chronic infections thwart development of immune cell memory
- Single episode of binge drinking can adversely affect health according to new UMMS study
Study finds large increase in type 1 and 2 diabetes among US youth
In a study that included data from more than three million children and adolescents from diverse geographic regions of the United States, researchers found that the prevalence of both type 1 and type 2 diabetes increased significantly between 2001 and 2009, according to the study in the May 7 issue of JAMA, a theme issue on child health. This issue is being released early to coincide with the Pediatric Academic Societies Annual Meeting.
Dana Dabelea, M.D., Ph.D., of the Colorado School of Public Health, Aurora, Colo., and Elizabeth J. Mayer-Davis, Ph.D., of the University of North Carolina, Chapel Hill, and colleagues with the SEARCH for Diabetes in Youth Study, examined whether the overall prevalence of type 1 and type 2 diabetes among U.S. youth has changed in recent years, and whether it changed by sex, age, and race/ethnicity. Despite concern about an “epidemic,” there have been limited data on trends regarding diabetes. “Understanding changes in prevalence according to population subgroups is important to inform clinicians about care that will be needed for the pediatric population living with diabetes and may provide direction for other studies designed to determine the causes of the observed changes,” the authors write.
The analysis included cases of physician-diagnosed type 1 diabetes in youth ages 0 through 19 years and type 2 diabetes in youth 10 through 19 years of age in 2001 and 2009. The study population came from five centers located in California, Colorado, Ohio, South Carolina, and Washington state, as well as data from selected American Indian reservations in Arizona and New Mexico.
In 2001, the prevalence of type 1 diabetes among a population of 3.3 million was 1.48 per 1,000, which increased to 1.93 per 1,000 among 3.4 million youth in 2009, which, after adjustment, indicated an increase of 21 percent over the 8-year period. The greatest prevalence increase was observed in youth 15 through 19 years of age. Increases were observed in both sexes and in white, black, Hispanic, and Asian Pacific Islander youth. “Historically, type l diabetes has been considered a disease that affects primarily white youth; however, our findings highlight the increasing burden of type l diabetes experienced by youth of minority racial/ethnic groups as well,” the authors write.
The overall prevalence of type 2 diabetes for youth ages 10 to 19 years increased by an estimated 30.5 percent between 2001 and 2009 (among a population of 1.7 million and 1.8 million youth, respectively). Increases occurred in white, Hispanic, and black youth, whereas no changes were found in Asian Pacific Islander and American Indian youth. A significant increase was seen in both sexes and all age-groups.
“The increases in prevalence reported herein are important because such youth with diabetes will enter adulthood with several years of disease duration, difficulty in treatment, an increased risk of early complications, and increased frequency of diabetes during reproductive years, which may further increase diabetes in the next generation,” the researchers write. “Further studies are required to determine the causes of these increases.”
Compound Formula Rehmannia alleviates dyskinesia in Parkinson’s disease
Levodopa is the preferred treatment for Parkinson’s disease in the clinic. However, long-term use of levodopa may lead to various motor complications, among which levodopa-induced dyskinesia is the most common, severely affecting patients’ quality of life. Dr. Jiancheng He and co-workers from Shanghai University of Traditional Chinese Medicine in China established a model of Parkinson’s disease dyskinesia in rats, and treated these animals with Compound Formula Rehmannia. They found that Compound Formula Rehmannia alleviates levodopa-induced dyskinesia in Parkinson’s disease by modulating neurotransmitter signaling in the corpus striatum. The relevant article has been published in the Neural Regeneration Research (Vol. 9, No. 4, 2014).
Low testosterone levels may indicate worsening of disease for men with prostate cancer
For men with low-risk prostate cancer, low levels of testosterone may indicate a worsening of their disease. That’s the conclusion of a new study published in BJU International. The findings may help physicians identify patients with low-risk prostate cancer who should receive aggressive anticancer treatment.
Men with prostate cancer that is not life threatening and is only slowly progressing, can often forego treatment and instead undergo active surveillance. This involves close monitoring to ensure that their disease does not become serious and jeopardize their health. Unfortunately, doctors currently have no reliable way of predicting which men will develop evidence of worsening or more aggressive disease during active surveillance.
Ignacio San Francisco, MD, of the Pontificia Universidad Católica de Chile, and his colleagues looked to see if testosterone levels might provide any indication. After following 154 men with low-risk prostate cancer for 38 months, the investigators found that low levels of free testosterone were significantly linked with an increased risk of developing more aggressive disease. They found no significant association with total testosterone concentrations, although there was a general trend towards increased risk with lower levels. Free testosterone comprises one to two percent of total testosterone and is considered a useful surrogate for the biologically active portion of circulating testosterone.
“These results suggest low levels of testosterone are associated with more aggressive prostate cancer. This contradicts long-held beliefs that high testosterone is risky for prostate cancer, and low testosterone is protective,” said Dr. San Francisco.
The results of this study provide valuable information to clinicians and their patients concerning risk factors for prostate cancer progression in men undergoing active surveillance. “In borderline cases, the presence of low values of free testosterone may help determine whether it is more prudent to initiate treatment rather than continue observation,” said Dr. San Francisco.
New cause of high blood pressure and heart disease discovered
05-05-2014 – Why phosphate rich foods can increase blood pressure and promote vascular calcifications has been discovered by scientists at the Vetmeduni Vienna. The key is the hormone, FGF23 (Fibroblast Growth Factor 23). When the level of FGF23 is raised, as through a high phosphate diet, calcium and sodium accumulate, putting strain on the cardiovascular system. The study appears today in the journal, EMBO Molecular Medicine.
Phosphate rich foods include processed cheese, Parmesan, cola, baking powder and most processed foods. Phosphates are widely used in the food industry as preservatives and pH stabilizers. When large quantities of phosphates are consumed, production of the FGF23 hormone is stimulated, which has a negative effect on the cardiovascular system. Reinhold Erben, the head of the Unit of Physiology, Pathophysiology and Biophysics at the Vetmeduni Vienna, warns that “our phosphate consumption is relevant for our state of health.”
Over 500 million people around the world suffer from chronic kidney disease. Clinical studies have shown that these patients often develop cardiovascular diseases such as high blood pressure and vascular calcification. Until now, the connection between renal disease, the accumulation of the hormone FGF23 which is produced in the bones, and cardiovascular disease was unclear.
FGF23 controls renal excretion of sodium, and so the blood pressure
The researchers showed that FGF23 has a so called sodium conserving effect, meaning it controls the reabsorption of filtered sodium in the kidneys. Mice lacking FGF23 excrete higher amounts of sodium in their urine, resulting in low blood pressure. Animals with high FGF23 levels show high levels of sodium in their blood, and in turn, high blood pressure.
A raised level of FGF23 puts increased strain on the heart. Reinhold Erben explains that, “In patients with chronic renal disease, both the phosphate levels and the levels of FGF23 are chronically high. This often leads to cardiovascular disease.
FGF23 controls calcium, and therefore vascular calcification
A second study, published by Erben’s group in mid-January in EMBO, showed that FGF23 also controls calcium levels. As with sodium, the calcium is filtered in the kidneys and reabsorbed back into the body. If this reabsorption does not take place, the body loses calcium. Too much FGF23 leads to increased take up of calcium by the kidneys, and results in vascular calcification. Olena Andrukhova, the leading author of both studies, is keen to stress that, “Patients with chronic kidney disease often also suffer from cardiovascular disease. Raised FGF23 levels are partly responsible for this. Our results for the first time are able to explain this connection.”
Feedback loop between kidneys and bones
The hormone FGF23 is formed in the bones and controls the excretion of phosphate via the kidneys. When there is too much phosphate present in the body, the FGF23 level rises which leads to the excretion of excess phosphate. If too much phosphate is ingested with food, or if the excretion process via the kidneys does not work correctly, phosphate and FGF23 levels increase. A dangerous spiral begins that can have serious consequences on the overall health.
New critical values of FGF23 in science
The newly discovered functions of the hormone FGF23 were, until recently, attributed to another protein, αKlotho. Several scientific publications had assumed αKlotho to be the crucial factor for calcium conservation in the kidneys. With their newly published work, Erben and his colleagues show for the first time that FGF23 is responsible for this function, and not αKlotho. However, αKlotho is essential for the FGF23 effects, because it acts as a co-receptor for FGF23. Andrukhova stresses that “The focus in science is increasingly shifting from αKlotho to FGF23. The level of FGF23 in kidney patients can even indicate their life expectancy. The inhibition of FGF23 or its pathway could be a possibility to bring cardiovascular disease and vascular calcification under control.”
Hypertension related to new cancer therapies — a new syndrome emerges
Mechanisms of VEGF inhibitor-induced hypertension need to be better understood and guidelines developed to improve management, say researchers in the Canadian Journal of Cardiology
Philadelphia, PA, May 5, 2014 – New cancer therapies, particularly agents that block vascular endothelial growth factor (VEGF) signaling, have improved the outlook for patients with some cancers and are now used as a first line therapy for some tumors. However, almost 100% of patients who take VEGF inhibitors (VEGFIs) develop high blood pressure, and a subset develops severe hypertension. The mechanisms underlying VEGF inhibitor-induced hypertension need to be better understood and there is a need for clear guidelines and improved management, say investigators in a review article published in the Canadian Journal of Cardiology.
“Exactly how VEGFIs cause hypertension is unknown. However, what is clear is that inhibition of VEGF in the vasculature directly increases blood pressure because hypertension develops acutely in response to VEGFIs and blood pressure returns to normal once the treatment is stopped,” says senior investigator Rhian M. Touyz, MD, PhD, of the Institute of Cardiovascular and Medical Sciences, University of Glasgow, Scotland.
Angiogenesis inhibitors are a new class of cancer drugs that are designed to prevent the formation of new blood vessels, thereby stopping or slowing the growth or spread of tumors. Angiogenesis requires the binding of signaling molecules, such as VEGF, to receptors on the surface of normal endothelial cells. When VEGF and other endothelial growth factors bind to their receptors on endothelial cells, signals within these cells are initiated that promote the growth and survival of new blood vessels, which are necessary for tumor growth. Angiogenesis inhibitors interfere with various steps in this process.
Increased blood pressure has been observed in every trial involving VEGFIs and is the most common cardiovascular complication; it has an associated increased risk of fatal adverse cardiovascular events. According to some studies, VEGFI-induced hypertension is not a side effect of treatment, but rather a mechanism-dependent on-target toxicity. This has led to the concept that hypertension might be indicative of effective VEGF inhibition and a positive antiangiogenic response, and as such could be a biomarker of a favorable outcome from VEGFI treatment. “This further adds to the challenges, because improved cancer responsiveness might thus be associated with potentially greater cardiovascular risk,” notes Dr. Touyz.
The exact factors that predispose to VEGFI-induced hypertension still remain to be established, say the investigators. However, risk factors that have been associated with VEGFI-induced hypertension include a previous history of hypertension, combination therapy with more than one anti-VEGFI, over 65 years of age, smoking, and possibly high cholesterol. Body mass index, renal function, race, a family history of hypertension, or cardiovascular disease do not seem to predict development of hypertension with VEGFI treatment.
The investigators recommend that management of hypertension in patients being treated with VEGFIs should be aimed at reducing the risk of short-term morbidity associated with hypertension while maintaining effective dosing of antiangiogenic therapy for optimal cancer treatment. Specific guidelines are not yet available for the management of VEGFI-induced hypertension, but expert opinion recommends that patients be fully assessed for hypertension and cardiovascular disease before VEGFI treatment, blood pressure is monitored frequently, and hypertension is aggressively treated to target (less than 140/90 mm Hg). Current treatment choices are based on clinical experience, with ACE inhibitors and dihydropyridine calcium channel blockers being the most commonly used antihypertensive drugs in VEGFI-induced hypertension.
“As VEGF inhibitors become more widely used and the number of older patients with cardiovascular risk factors and pre-existing hypertension are treated with these drugs, the need to better understand the molecular mechanisms underlying VEGF inhibitor-induced hypertension and the risk factors predisposing to this condition are imperative, so that clear guidelines and improved management can be instituted,” concludes Dr.Touyz.
Novel antioxidant makes old arteries seem young again, CU-Boulder study finds
An antioxidant that targets specific cell structures—mitochondria—may be able to reverse some of the negative effects of aging on arteries, reducing the risk of heart disease, according to a new study by the University of Colorado Boulder.
When the research team gave old mice—the equivalent of 70- to 80-year-old humans—water containing an antioxidant known as MitoQ for four weeks, their arteries functioned as well as the arteries of mice with an equivalent human age of just 25 to 35 years.
The researchers believe that MitoQ affects the endothelium, a thin layer of cells that lines our blood vessels. One of the many functions of the endothelium is to help arteries dilate when necessary. As people age, the endothelium is less able to trigger dilation and this leads to a greater susceptibility to cardiovascular disease.
“One of the hallmarks of primary aging is endothelial dysfunction,” said Rachel Gioscia-Ryan, a doctoral student in CU-Boulder’s Department of Integrative Physiology and lead author of the new study. “MitoQ completely restored endothelial function in the old mice. They looked like young mice.”
The study, published in the Journal of Physiology, was funded by the National Institute on Aging, one of the 27 institutes and centers of the National Institutes of Health and a leader in the scientific effort to understand the nature of aging.
To trigger blood vessel dilation, the endothelium makes nitric oxide. As we age, the nitric oxide meant to cause dilation is increasingly destroyed by reactive oxygen species such as superoxide, which are produced by many components of our body’s own cells, including organelles called mitochondria.
In a double-whammy, superoxide also reacts directly with the enzyme that makes nitric oxide, reducing the amount of nitric oxide being produced to begin with. All of this means less blood vessel dilation.
Even in the young and healthy, mitochondria produce superoxide, which is necessary in low levels to maintain important cellular functions. Superoxide is kept in check by the body’s own antioxidants, which combine with superoxide to make it less reactive and prevent oxidative damage to cells.
“You have this kind of balance, but with aging there is this shift,” said Gioscia-Ryan, who works in Professor Douglas Seals’ Integrative Physiology of Aging Laboratory at CU-Boulder. “There become way more reactive oxygen species than your antioxidant defenses can handle.”
That phenomenon, known as oxidative stress, occurs when the cells of older adults begin to produce too much superoxide and other reactive oxygen species. Mitochondria are a major source of superoxide in aging cells. The increased superoxide not only interacts with nitric oxide and the endothelium, but can also attack the mitochondria themselves. The damaged mitochondria become increasingly dysfunctional, producing even more reactive oxygen species and creating an undesirable cycle.
Past studies have looked at whether taking antioxidant supplements long term could improve vascular function in patients with cardiovascular disease by restoring balance to the levels of superoxide, but they’ve largely shown that the strategy isn’t effective.
This new study differs because it uses an antioxidant that specifically targets mitochondria. Biochemists manufactured MitoQ by adding a molecule to ubiquinone (also known as coenzyme Q10), a naturally occurring antioxidant. The additional molecule makes the ubiquinone become concentrated in mitochondria.
“The question is, ‘Why aren’t we all just taking a bunch of vitamin C?” Gioscia-Ryan said. “Scientists think that, taken orally, antioxidants like vitamin C aren’t getting to the places where the reactive oxygen species are being made. MitoQ basically tracks right to the mitochondria.”
The findings of the study indicate that the strategy of specifically targeting the mitochondria may be effective for improving the function of arteries as we age. In addition to improving endothelial function, the MitoQ treatment increased levels of nitric oxide, reduced oxidative stress and improved the health of the mitochondria in the arteries of old mice.
Eating more fruits, vegetables may cut stroke risk worldwide
American Heart Association Rapid Access Journal Report
Eating more fruits and vegetables may reduce the risk of stroke worldwide, according to new research in the American Heart Association’s journal Stroke.
Researchers conducted a meta-analysis of 20 studies published over the last 19 years to assess the effects of fruit and vegetable consumption on risk of stroke globally. The combined studies involved 760,629 men and women who had 16,981 strokes.
Stroke risk decreased by 32 percent with every 200 grams of fruit consumed each day and 11 percent with every 200 grams of vegetables consumed each day.
“Improving diet and lifestyle is critical for heart and stroke risk reduction in the general population,” said Yan Qu, M.D., the study’s senior author, director of the intensive care unit at Qingdao Municipal Hospital and professor at the Medical College of Qingdao University in Qingdao, China. “In particular, a diet rich in fruits and vegetables is highly recommended because it meets micronutrient and macronutrient and fiber requirements without adding substantially to overall energy requirements.”
Macronutrients (carbohydrates, protein and fat) provide calories or energy. Our bodies need smaller amounts of micronutrients such as vitamins and minerals.
The researcher cited studies demonstrating that high fruit and vegetable consumption can lower blood pressure and improve microvascular function. It has favorable effects on body mass index, waist circumference, cholesterol, inflammation and oxidative stress.
The beneficial effects of fruits and vegetables applied consistently to men and women, stroke outcome and by type of stroke (caused by clot or bleeding). Researchers found no significant difference in the effect on age (younger or older than 55).
The researchers adjusted the study findings for factors such as smoking, alcohol, blood pressure, cholesterol, physical activity, body mass index and other dietary variables.
Researchers combined the results of six studies from the United States, eight from Europe and six from Asia (China and Japan). They note that low fruit and vegetable consumption is prevalent worldwide, and especially in low- and middle-income countries.
Increasing the consumption of fruits and vegetables up to 600 grams each day could reduce the burden of ischemic stroke by 19 percent globally, according to the World Health Organization.
In China, stroke is the leading cause of death, with an estimated 1.7 million people dying in 2010. In the United States, stroke is the No. 4 cause of death and a leading cause of disability.
The American Heart Association advises the average adult to eat four to five servings each of fruits and vegetables daily, based on a 2,000-calorie diet. A diet rich in a variety of colors and types of vegetables and fruits is a way of getting important nutrients that most people don’t get enough of, including vitamins, minerals, and dietary fiber. They are also naturally low in saturated fat.
Gluten-free diet reduces risk of type 1 diabetes in mice
New experiments on mice show, that mouse mothers can protect their pups from developing type 1 diabetes by eating a gluten-free diet. According to preliminary studies by reseachers at the University of Copenhagen, the findings may apply to humans.
More than 1% of the Danish population has type 1 diabetes, one of the highest incidence rates in the world. New experiments on mice now show a correlation between the health of the pups and their mothers eating a gluten-free diet. Our hope is that the disease may be prevented through simple dietary changes, the researchers say.
“Preliminary tests show that a gluten-free diet in humans has a positive effect on children with newly diagnosed type 1 diabetes. We therefore hope that a gluten-free diet during pregnancy and lactation may be enough to protect high-risk children from developing diabetes later in life,” says assistant professor Camilla Hartmann Friis Hansen from the Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences.
The findings have recently been published in the recognised journal Diabetes.
14 years of research into gluten-free diet
Findings from experiments on mice are not necessarily applicable to humans, but in this case we have grounds for optimism, says co-writer on the study professor Axel Kornerup from the Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences.
“Early intervention makes a lot of sense because type 1 diabetes develops early in life. We also know from existing experiments that a gluten-free diet has a beneficial effect on type 1 diabetes,” he says.
Experiments of this type have been going on since 1999, originally initiated by Professor Karsten Buschard from the Bartholin Institute at Rigshospitalet in Copenhagen, another co-writer on the study.
“This new study beautifully substantiates our research into a gluten-free diet as an effective weapon against type 1 diabetes,” Karsten Buschard explains.
Gluten-free diet affects bacteria
The experiment showed that the diet changed the intestinal bacteria in both the mother and the pups. The intestinal flora plays an important role for the development of the immune system as well as the development of type 1 diabetes, and the study suggests that the protective effect of a gluten-free diet can be ascribed to certain intestinal bacteria. The advantage of the gluten-free diet is that the only side-effect seems to be the inconvenience of having to avoid gluten, but there is no certain evidence of the effect or side-effects.
“We have not been able to start a large-scale clinical test to either prove or disprove our hypothesis about the gluten-free diet,” says Karsten Buschard.
Assistant Professor Camilla Hartmann Friis Hansen is hoping that it will be possible to continue the work.
“If we find out how gluten or certain intestinal bacteria modify the immune system and the beta-cell physiology, this knowledge can be used to develop new treatments,” she says.
Low-carbohydrate diet reduced inflammation
A low-carbohydrate diet, but not a low-fat diet, reduces inflammation in patients with type 2 diabetes, according to research at Linköping University in Sweden.
It is known that patients with type 2 diabetes have higher levels of inflammation than those who do not have the disease, and it is believed that this may contribute to a higher risk of cardiovascular disease and other complications. In a clinical trial at Linköping University a low-carbohydrate diet was compared with a traditional low-fat diet in 61 patients with type 2 diabetes. Only patients in the low-carbohydrate group exhibited reduced levels of inflammatory markers in blood, despite the fact that weight loss was similar in both groups.
The trial was conducted over a two year period and was led by Dr Hans Guldbrand and Professor Fredrik H Nyström. The patients were randomly assigned to a low-carbohydrate diet or a traditional low-fat diet and were given menu suggestions and advices by a dietician during three occasions of the first year. The effects on blood glucose, blood lipids and weight were recently published in the journal Diabetologia 2012.
In the present study, published in the journal Annals of Medicine the effects of diets on inflammation were studied in collaboration with cardiologist Professor Lena Jonasson. Compared with healthy individuals without diabetes, the patients exhibited significantly higher levels of inflammatory markers at baseline. New analyses were performed after six months, i.e. when adherence to the two diets was greatest and the weight loss had reached maximum. Weight reduction in both groups was similar, around 4 kg, whereas glucose levels decreased more in the low-carbohydrate group (who had lowered their carbohydrate intake to 25% of total energy intake). After six months, inflammation was significantly reduced in the low-carbohydrate group while no changes were observed in the low-fat diet group.
In summary, the presented clinical trial resulted in a similar weight loss comparing low-carbohydrate diet and low-fat diet, but only the low-carbohydrate diet had a favourable impact on inflammation in patients with type 2 diabetes.
Calcium supplements not associated with increased risk of cardiovascular disease in women
Boston, MA – Calcium supplements are widely taken by women for bone health. Previous studies have suggested that calcium supplements may increase risk of cardiovascular disease, but the data has been inconsistent. A new study by researchers at Brigham and Women’s Hospital (BWH) did not find that calcium supplement intake increases risk of cardiovascular disease in women.
The study is published online this month in Osteoporosis International.
Researchers examined supplemental calcium use and incident cardiovascular disease in a prospective cohort study of 74,245 women in the Nurses’ Health Study. The women did not have cardiovascular disease or cancer at the start of the study. They were followed for 24 years to document risk of developing heart attack and stroke. Calcium supplement intake was assessed every four years.
“Our study has several distinct strengths compared to prior studies including the large number of participants, long-term follow-up, large number of cardiovascular events that were confirmed by medical record review, detailed information about diet and other cardiovascular disease risk factors, and repeated assessment of calcium supplement use over the 24-year follow up period,” said Julie Paik, MD, MPH, BWH Channing Division of Network Medicine, Department of Medicine, lead study author.
The researchers found that at the start of the study, women who took calcium supplements had higher levels of physical activity, smoked less, and had lower trans fat intake compared to women who did not take calcium supplements. During the 24 years of follow-up, there were 2,709 heart attacks and 1,856 strokes.
“Based on our findings, additional prospective cohort studies examining potential cardiovascular disease risk associated with calcium supplement use are needed,” said Paik. “Future randomized trials of calcium supplementation, if conducted, should be designed to optimize assessment of cardiovascular events.”
Fourfold increase in the rate of diagnosed cases of celiac disease in the UK
Coeliac UK, the national charity for coeliac disease announces today, 12th May 2014, new research from the University of Nottingham that has found a fourfold increase in the rate of diagnosed cases of coeliac disease in the United Kingdom over the past two decades, but, still three quarters of people with coeliac disease remain undiagnosed. ¹
The National Institute of Health & Care Excellence (NICE) previously estimated that only 10 – 15% of those with coeliac disease had been diagnosed, however, this latest research by Dr Joe West from University of Nottingham, funded by Coeliac UK and CORE has shown that the level of diagnosis has increased to 24%.
Coeliac disease is an autoimmune disease caused by intolerance to gluten. Left untreated it may lead to infertility, osteoporosis and small bowel cancer. 1 in 100 people in the UK have coeliac disease, with the prevalence rising to 1 in 10 for close family members
The only treatment for coeliac disease is a strict, lifelong gluten-free diet. Gluten is a protein found in wheat, barley and rye and, once diagnosed, people with coeliac disease need to eliminate all gluten-containing foods and make sure they only eat gluten-free varieties.
Researchers identified the number of people diagnosed during the study period using the diagnostic codes for coeliac disease recorded in the Clinical Practice Research Datalink (1990-2011).
This research, published by The American Journal of Gastroenterology comes out as the charity celebrates its annual Awareness campaign which this year is entitled the ‘Gluten-free Guarantee’ and aims to improve availability of gluten-free foods in stores across the UK.
Sarah Sleet, Chief Executive of Coeliac UK said: “This latest research shows that nearly a quarter of people with coeliac disease have now been diagnosed and gives an up to date picture of the diagnosis levels across the UK. Of course, increasing numbers with a diagnosis is good news and will inevitably mean that there will be an increased demand for gluten-free products in supermarkets. But the three quarters undiagnosed is around 500,000 people – a shocking statistic that needs urgent action.”
From 12-18 May 2014 the charity is asking people across the UK to support the ‘Gluten-free Guarantee’ which asks supermarkets to commit to have in stock eight core items of gluten-free food, making it easier for people with the condition to manage their gluten-free diet, which is their only treatment.
“Can you imagine going into your local supermarket and there is no bread you can eat, not one loaf not one slice? And when you check out the pasta, cereal or flour again there is nothing available on the shelf which means you have to trawl around two or three stores in order to be able to find your staple foods. This is not about your preferred brand but about the major supermarkets ensuring that they have sufficient stock in all their stores whatever their size for this growing market of people who depend on gluten-free food for their health.”
The symptoms of coeliac disease range from mild to severe and can vary between individuals. Not everyone with coeliac disease experiences gut related symptoms; any area of the body can be affected. Symptoms can include ongoing gut problems such as bloating, abdominal pain, nausea, constipation, diarrhoea, and wind, and other common symptoms include extreme tiredness, anaemia, headaches and mouth ulcers, weight loss (but not in all cases), skin problems, depression, and joint or bone pain.
Understanding aspirin’s effect on wound healing offers hope for treating chronic wounds
In addition to its known capacity to promote bleeding events, aspirin also inhibits wound healing. New research published in The Journal of Experimental Medicine now describes how aspirin acts on key skin cells called keratinocytes, delaying skin repair at wound sites. A better understanding of this process offers hope for the development of drugs to encourage wounds to heal.
The public health impact of chronic wounds is significant, affecting 6.5 million people in the US alone. Chronic wounds, a common complication of diabetes, are an increasing healthcare burden due to the rising incidence rates for obesity and diabetes. Wound healing is a complex process that is dependent on the restoration of the epithelial layer, the outermost layer of the skin, over the wound surface. Skin cells called keratinocytes play an important role in this process; when keratinocyte migration across the wound is defective, wounds such as diabetic ulcers cannot heal and become chronic wounds. However, we do not fully understand how keratinocyte movement during wound healing is regulated.
Researchers from Japan were prompted to investigate the role of a molecule called 12-HHT and its receptor BLT2 in wound healing; 12-HHT is produced during blood coagulation following skin injury and BLT2 is found on the surface of keratinocytes. The researchers showed that 12-HHT promotes the re-formation of the epithelial layer at wound sites by enhancing the migration of keratinocytes. They discovered that high dose aspirin, the most commonly used nonsteroidal anti-inflammatory drug, delays wound healing by reducing the production of 12-HHT. The researchers also found that a synthetic mimic of BLT2 accelerated wound healing in diabetic mice (a model that is commonly used to investigate delayed wound healing).
“This study describes a novel mechanism for aspirin’s effect in delaying wound healing and suggests that aspirin should be used with caution in patients with chronic wounds,” says lead author Takehiko Yokomizo.
Further work will be required to establish whether optimal treatment for wound healing might require a combination of approaches, such as BLT2 agonists together with growth factors to promote the number of wound-healing cells at the wound site, but this study offers hope that it may be possible to develop drugs that promote the healing of chronic wounds in humans.
Brain may never fully recover from exposure to paint, glue, degreasers
MINNEAPOLIS – People who are exposed to paint, glue or degreaser fumes at work may experience memory and thinking problems in retirement, decades after their exposure, according to a study published in the May 13, 2014, print issue of Neurology®, the medical journal of the American Academy of Neurology.
“Our findings are particularly important because exposure to solvents is very common, even in industrialized countries like the United States.” said study author Erika L. Sabbath, ScD, of Harvard School of Public Health in Boston. “Solvents pose a real risk to the present and future cognitive health of workers, and as retirement ages go up, the length of time that people are exposed is going up, too.”
The study involved 2,143 retirees from the French national utility company. Researchers assessed the workers’ lifetime exposure to chlorinated solvents, petroleum solvents, and benzene, including the timing of last exposure and lifetime dosage. Benzene is used to make plastics, rubber, dye, detergents and other synthetic materials. Chlorinated solvents can be found in dry cleaning solutions, engine cleaners, paint removers and degreasers. Petroleum solvents are used in carpet glue, furniture polishes, paint, paint thinner and varnish. Of the participants, 26 percent were exposed to benzene, 33 percent to chlorinated solvents and 25 percent to petroleum solvents.
Participants took eight tests of their memory and thinking skills an average of 10 years after they had retired, when they were an average age of 66. A total of 59 percent of the participants had impairment on one to three of the eight tests; 23 percent had impairment on four or more tests; 18 percent had no impaired scores.
The average lifetime solvent exposure was determined based on historical company records, and the participants were categorized as having no exposure, moderate exposure if they had less than the average and high exposure if they had higher than the average. They were also divided by when the last exposure occurred, with those last exposed from 12 to 30 years prior to the testing considered as recent exposure and those last exposed 31 to 50 years prior considered as more distant exposure.
The research found that people with high, recent exposure to solvents were at greatest risk for memory and thinking deficits. For example, those with high, recent exposure to chlorinated solvents were 65 percent more likely to have impaired scores on tests of memory and visual attention and task switching than those who were not exposed to solvents. The results remained the same after accounting for factors such as education level, age, smoking and alcohol consumption.
“The people with high exposure within the last 12 to 30 years showed impairment in almost all areas of memory and thinking, including those not usually associated with solvent exposure,” Sabbath said. “But what was really striking was that we also saw some cognitive problems in those who had been highly exposed much longer ago, up to 50 years before testing. This suggests that time may not fully lessen the effect of solvent exposure on some memory and cognitive skills when lifetime exposure is high.”
Sabbath said the results may have implications for policies on workplace solvent exposure limits. “Of course, the first goal is protecting the cognitive health of individual workers. But protecting workers from exposure could also benefit organizations, payers, and society by reducing workers’ post-retirement health care costs and enabling them to work longer,” said Sabbath. “That said, retired workers who have had prolonged exposure to solvents during their career may benefit from regular cognitive screening to catch problems early, screening and treatment for heart problems that can affect cognitive health, or mentally stimulating activities like learning new skills.”
Smart drugs pose special risks to the developing brain of young people
Over a million American students misuse prescription drugs or take illegal stimulants to increase their attention span, memory, and capacity to stay awake. Such “smart drugs” become more and more popular due to peer pressure, stricter academic requirements, and the tight job market. But young people who misuse them risk long-term impairments to brain function, warn Kimberly Urban at the University of Delaware and Wen-Jun Gao at Drexel University College of Medicine, USA, in a NIH-funded review published in the open-access journal Frontiers in Systems Neuroscience.
The latest research on the potential lasting side-effects of the most important smart drugs on the uniquely delicate, developing brain of young people was reviewed. It was found that any short-term boost in mental performance due to smart drugs may come at a heavy cost: a long-term decrease in brain plasticity, necessary for task switching, planning ahead, and adaptive flexibility in behavior.
Special risks for young brains
Methylphenidate is the most popular smart drug among kids today and often sold on the black market. It was originally developed as a prescription-only drug (sold as Ritalin and Concerta) to treat ADHD, and works by increasing the level of neurotransmitter in the nervous system. Around 1.3 million American teenagers misused or abused methylphenidate without prescription in the previous month, according to The Partnership at Drugfree.org and the MetLife Foundation.
Trials on rats have shown that young, developing brains are particularly sensitive to methylphenidate: even low dosages early in life can reduce nerve activity, working memory, and the ability to quickly switch between tasks and behaviors. Such mental flexibility is important for complex motoric learning, interpersonal skills, and work performance.
Another popular smart drug is modafinil, sold under the name Proviigil against narcolepsy and other sleep disorders. Believed to work by raising the levels of dopamine in between synapses of brain nerve cells, it can boost memory as well as the ability to work with numbers and do other mental tasks. But research indicates that modafinil could have similar long-term undesired effects as methylphenidate on the developing brain.
New smart drugs also pose risks
Not yet widely used are ampakines, an emerging class of drugs currently studied by the US military with the aim of increasing alertness in soldiers. Ampakines bind to so-called AMPA receptor molecules in the nervous system and boost the response of nerve cells and strengthen connections between them. Known to improve memory and cognition in rats and healthy humans volunteers, ampakines are often considered to be relatively safe potential smart drugs. But they are not without dangers for young people: uncontrolled use might over-excite the nervous system, damaging or killing nerve cells, caution the authors.
Many “known unknowns”
More research on the long-term effects of methylphenidate, modafinil, ampakines, and other smart drugs, especially in young people, is urgently needed, the authors caution.
“What’s safe for adults is not necessarily safe for kids,” warns Urban. “The human brain continues to develop until our late twenties or early thirties. Young people are especially prone to abuse smart drugs, but also more vulnerable to any side-effects. We simply don’t know enough about the long-term effects of these drugs on the developing brain to conclude they are safe.”
Forgiving a Wrong May Actually Make It Easier to Forget
We’re often told to “forgive and forget” the wrongs that we suffer — it turns out that there may be some scientific truth behind the common saying. A study from researchers at the University of St. Andrews in Scotland shows that the details of a transgression are more susceptible to forgetting when that transgression has been forgiven.
The findings are published in Psychological Science, a journal of the Association for Psychological Science.
“It is well established that learning to forgive others can have positive benefits for an individual’s physical and mental health,” says Saima Noreen, lead author of the study. “The ability to forget upsetting memories may provide an effective coping strategy that enables people to move on with their lives.”
From the perspective of cognitive science, overcoming strong negative emotions toward the person who did us wrong and quashing impulses for retribution or vengeance — processes that are critical to forgiveness — may be seen as a function of executive control.
And research suggests that this executive control is also involved in our ability to forget something when we’re motivated to forget it.
Noreen decided to examine whether this same cognitive mechanism might form a link between forgiveness and forgetting.
The study, conducted with colleagues Malcolm MacLeod and Raynette Bierman, involved participants reading 40 scenarios that contained hypothetical wrongdoings, including infidelity, slander, and theft. They were asked to evaluate the transgression and say whether, as the victim, they would forgive the misdeed.
About 1 to 2 weeks later, they read a subset of the scenarios again, but this time each scenario was paired with a neutral cue word. After learning the scenario-cue pairings, the participants were presented with some of the cue words, written in either red or green, and were instructed to recall the related scenario when the cue word was green, and to avoid thinking about the scenario when the cue word was red.
This procedure, often used in memory research, essentially trains people to forget specific information or details. The researchers wanted to see whether forgiveness might affect the forgetting process.
For transgressions they had forgiven in the first session, participants showed more forgetting when they had been instructed to forget the scenario in the second session, compared to when they had been given no specific instructions.
In contrast, participants showed no forgetting for scenarios they had not forgiven, even when they had been told to forget them.
Together, these findings suggest that forgiveness may facilitate intentional forgetting by helping individuals to suppress details about the transgressions perpetrated against them.
So, while true forgiveness may be difficult to accomplish, the findings suggest that once the transgression has been forgiven forgetting may become easier as a result.
“This research is only coming into fruition, and it’s likely that the relationship between forgiveness and forgetting is bi-directional and far more complex over longer periods of time,” Noreen says. “We hope that, in time, new fields of enquiry may combine forgetting- and forgiveness-based interventions that might, in turn, give rise to powerful therapeutic tools that will enable people to “forgive and forget” more effectively.”
PCB increases harmful effects of smoking
It is well known that exposure to asbestos or radon drastically increases the injurious effects of smoking. In the present study, led by Uppsala University, the scientists have investigated whether high blood levels of the environmental contaminant PCB (polychlorinated biphenyls) reinforces the harmful effect of smoking.
The study was performed within the framework of the so-called PIVUS study, which comprehends some 1,000 70-year-old men and women in Uppsala. The results show that the risk of having died at the 8-year follow-up was 40 per cent higher for smokers with low levels of PCB in their blood compared with non-smokers. For smokers with high levels of PCB, the risk was fully 640 per cent higher.
Also in former smokers the risk of dying was considerably higher among those who had high levels of PCB in their blood compared with those who had low levels (370 per cent greater risk, compared with 20 per cent). On the other hand, no elevated mortality was found among those who had never smoked.
– These data show that exposure to PCB increases the risk dramatically in both smokers and former smokers. For non-smokers, no elevated risk was found, at any rate not after eight years. More studies are needed to clarify the risks for this group, says Lars Lind, professor of cardiovascular epidemiology at the Department of Medical Sciences, Uppsala University.
PCBs (Polychlorinated biphenyls) are a group of environmental contaminants that were banned nearly 20 years ago. But since they accumulate in the food chain and remain in the human body for a very long time, high levels can still be found in a majority of the population in Sweden and most other industrialised countries. High levels of PCBs have previously been shown to be linked to poor heart function, and for a number of risk factors for heart problems, such as obesity, diabetes and high blood pressure.
Zinc supplementation boosts immune system in children, Cochrane Review finds
Zinc supplements reduce diarrhoea and other infections in malnourished children, and may prevent death, according to a new study published in The Cochrane Library. The study is the first Cochrane systematic review to focus on zinc as a means to prevent childhood death, including deaths caused by diarrhoea, one of the biggest killers of under-fives.
Zinc is a micronutrient with important roles in growth and in the immune, nervous and reproductive systems. The human body cannot make it, so it has to come from our diet. It is estimated that more than 1 in 6 people globally are deficient in zinc and that around 1 in every 58 deaths in children under five is related to zinc deficiency. Zinc deficiency is common in Southeast Asia, sub-Saharan Africa and parts of Latin America.
The authors were interested in whether zinc supplements could reduce childhood death and disease, and help support growth. They reviewed data from 80 trials involving 205,401 children aged six months to twelve years, mostly in low and middle income countries. Overall, they concluded that zinc supplementation could benefit children as part of wider programmes to address public health and nutrition challenges in these countries.
“We should remember that supplements are not a substitute for a well-balanced diet,” said senior researcher Professor Zulﬁqar Bhutta from the Center of Excellence in Women and Child Health, Aga Khan University, Karachi, Pakistan, and Sick Kids Center for Global Child Health, Toronto, Canada. “However, in countries where zinc deficiency is common, supplements may help to reduce child deaths and related diseases in the short-term.”
Those children who took zinc were less likely to suffer a bout of diarrhoea, and when the researchers looked at growth differences, they saw that children who were given zinc were slightly taller by the end of the trials compared to those who did not. However, healthy eating is more important for growth. “Eating foods with balanced energy and protein and multiple micronutrients would probably have a larger effect for many malnourished children,” said Evan Mayo-Wilson, the lead author based at the Johns Hopkins University Bloomberg School of Public Health in Baltimore, Maryland.
Although zinc supplements were associated with an increase in vomiting, the researchers think that overall the benefits of giving zinc outweigh the harms.
Dr David Tovey, Editor-in-Chief, Cochrane, said, “Policymakers in low and middle income countries need evidence that directly addresses the needs of their own health services. This comprehensive review makes a very valuable contribution to the evidence base around interventions may make an important contribution to improving Global Health.”
Sugar implicated in cardiovascular disease risk independent of weight gain
Researchers from New Zealand’s University of Otago have uncovered evidence that sugar has a direct effect on risk factors for heart disease, and is likely to impact on blood pressure, independent of weight gain.
Research Fellow with Otago’s Department of Human Nutrition Dr Lisa Te Morenga, Professor Jim Mann and colleagues have conducted a review and meta-analysis of all international studies that compared the effects of higher versus lower added sugar consumption on blood pressure and lipids (blood fats or cholesterol) – both of which are important cardiovascular risk-factors.
They located dietary intervention trials published in English-speaking journals between 1965 and 2013, comparing diets where the only intended differences were the amount of sugars and non-sugar carbohydrates consumed by the participants, and which measured the effects of these diets on lipids and blood pressure. They found 37 trials reporting effects on lipids and 12 reporting effects on blood pressure. The findings from the individual trials were then pooled to determine the overall effects from all the studies.
“Our analysis confirmed that sugars contribute to cardiovascular risk, independent of the effect of sugars on body weight,” says Dr Te Morenga.
“Although the effects of sugars on blood pressure and lipids are relatively modest, our findings support public health recommendations to reduce added sugar in our diets as one of the measures which might be expected to reduce the global burden of cardiovascular diseases.”
Dr Te Morenga says previous research showed that there did not appear to be any special metabolic effect of sugars making people more likely to gain weight on high-sugar diets compared with low sugar diets when the total amount of carbohydrates and energy remains the same.
“However our latest study did find significant effects of sugars on lipids and blood pressure among these types of energy-controlled studies. This suggests that our bodies handle sugar differently to other types of carbohydrates.”
“We were also relatively surprised that there was a positive association between sugars and cardiometabolic risk factors given that a large body of the research which met our inclusion criteria is funded by the food industry. This is because such trials are less likely to find a significant association between sugars and health outcomes.
“In subgroup analyses we showed that by excluding the trials funded by the food/sugar industry, we found larger effects of sugar on lipids and blood pressure.”
She adds that the release of their findings online in the American Journal of Clinical Nutrition is very timely as national and international organisations are considering recommendations on safe dietary sugar intakes.
“Our work provides further evidence to support these recommendations which have been disputed by the food industry,” she says.
While there is still a need for further longer term well-powered studies looking at the effects of sugars on various health outcomes, it is becoming increasingly difficult for the food industry to continue to claim that liberal sugar consumption is risk free.
Dr Te Morenga says that anti-sugar researchers have claimed that eating too much sugar causes numerous harms, including cardiovascular risk.
“But their evidence has been based largely on animal studies or highly controlled clinical trials involving unrealistic diets. However, until now the evidence relating to cardiovascular risk factors from sugar in human studies, and involving relatively normal diets, was hard to make sense of.”
‘Bystander’ chronic infections thwart development of immune cell memory
Implications for improving efficacy of vaccine campaigns in regions with chronic, infectious diseases
PHILADELPHIA – Studies of vaccine programs in the developing world have revealed that individuals with chronic infections such as malaria and hepatitis tend to be less likely to develop the fullest possible immunity benefits from vaccines for unrelated illnesses. The underlying mechanisms for that impairment, however, are unclear, and distinguishing these so-called “bystander” effects on priming the immune system to fight future assaults versus development of immunological memory has been challenging.
A team from the Perelman School of Medicine at the University of Pennsylvania found that chronic bystander viral or parasitic infections – which are models for human infections like hepatitis, malaria, and parasitic worms – impaired the development of memory T cells in mouse models of long-term infection.
The effect of bystander infections also extended beyond mice. The researchers generated signatures of transcribed genes of cytomegalovirus-specific T cells from people with chronic hepatitis C infection and healthy controls. The gene-expression profiles of these two groups showed a clear impact of bystander chronic infection on T cells, including a difference in expression of many key T-cell memory-related genes. The findings are published this week in Immunity.
“Co-infections can result in poor immunity for other invading microbes and also vaccines,” says senior author E. John Wherry, PhD, director, Institute for Immunology and associate professor of Microbiology. “We now understand one of the main reasons: failure to develop immune memory capable of responding upon new infections.”
Immune memory, the hallmark of protective immunity against intracellular pathogens, is what keeps humans from being reinfected by a microbe to which they have already been exposed. Some immune cells are long-lived and active against whatever they were originally triggered by.
“If a person in the developing world gets a vaccine, and they harbor unrelated infections, such as malaria, tuberculosis, hepatitis B or C, and other parasitic infections, will this person have effective immune memory to the vaccine?” asks Wherry. “Our study has major relevance for applying vaccines in the developing world where co-infections might radically alter the type and quality of immunity generated by vaccines.”
Wherry cites vaccine campaigns for rotavirus and polio virus in the developing world in which people who were vaccinated had only 50 percent efficacy compared to 80 to 90 percent in the developed world for the same vaccine. Vaccine efficacy is the incidence of people who are vaccinated and get disease versus an unvaccinated control group.
The effects of bystander infection on immune memory cell development seen in the current study were independent of initial priming of the immune system by other pathogens and were associated with a molecular signature of chronic inflammation. Chronic inflammation reduced the number of bystander T cells, their memory development, and their ability to protect from a challenge infection.
The team concluded that exposure to prolonged bystander inflammation impairs the transition of effector T cells to memory T cells. In other words, bystander chronic infections prevent the critical ability of the immune response to “stand down” and preserve responsive cells for future encounters with the same infection.
These data have important implications for vaccines for the developing world where co-infections are common and also for vaccines and immune therapies in patients with chronic inflammatory diseases. Specifically, working to treat co-infections — via anti-parasite treatment in developing countries, for example — prior to vaccines or treatment with anti-inflammatory agents at the right times may improve long-term immunity in some settings.
Single episode of binge drinking can adversely affect health according to new UMMS study
Increase in endotoxins after heavy drinking leads to production of immune cells involved in fever, inflammation and tissue destruction
WORCESTER, MA – It only takes one time. That’s the message of a new study by scientists at the University of Massachusetts Medical School on binge drinking. Their research found that a single episode of binge drinking can have significant negative health effects resulting in bacteria leaking from the gut, leading to increased levels of toxins in the blood. Published online in PLOS ONE, the study showed that these bacterial toxins, called endotoxins, caused the body to produce immune cells involved in fever, inflammation, and tissue destruction.
“We found that a single alcohol binge can elicit an immune response, potentially impacting the health of an otherwise healthy individual,” said lead author Gyongyi Szabo, MD, PhD, professor of medicine, vice chair of the Department of Medicine and associate dean for clinical and translational sciences at UMMS. “Our observations suggest that an alcohol binge is more dangerous than previously thought.”
Binge drinking is defined by National Institute on Alcohol Abuse and Alcoholism (NIAAA) as a pattern of drinking alcohol that brings blood alcohol concentration (BAC) to 0.08g/dL or above. For a typical adult, this corresponds with consuming five or more drinks for men, or four or more drinks for women, in about two hours, depending on body weight.
Binge drinking is known to pose safety risks associated with car crashes and injuries. Over the long term, binge drinking can damage the liver and other organs, but this is key evidence that a single alcohol binge can cause damaging health effects such as bacterial leakage from the gut into the blood stream, according to a statement released by George Koob, PhD, director of the NIAAA.
To assess the impact of binge drinking, 11 men and 14 women were given enough alcohol to raise their blood alcohol levels to at least .08 g/dL within an hour. Blood samples were then taken every 30 minutes for four hours after and again 24 hours later.
Szabo and colleagues found that the alcohol binge resulted in a rapid increase in endotoxin levels in the blood. Endotoxins are toxins contained in the cell wall of certain bacteria that are released when the cell is destroyed. They also found evidence of bacterial DNA in the bloodstream, showing that bacteria had permeated the gut. Compared to men, women had higher blood alcohol levels and circulating endotoxin levels.
Earlier studies have tied chronic alcohol use to increased gut permeability, wherein potentially harmful products can travel through the intestinal wall and be carried to other parts of the body. Greater gut permeability and increased endotoxin levels have been linked to many of the health issues related to chronic drinking, including alcoholic liver disease.