New blood cells fight brain inflammation

Hyperactivity of our immune system can cause a state of chronic inflammation. If chronic, the inflammation will affect our body and result in disease. In the devastating disease multiple sclerosis, hyperactivity of immune cells called T-cells induce chronic inflammation and degeneration of the brain. Researchers at BRIC, the University of Copenhagen, have identified a new type of regulatory blood cells that can combat such hyperactive T-cells in blood from patients with multiple sclerosis. By stimulating the regulatory blood cells, the researchers significantly decreased the level of brain inflammation and disease in a biological model. The results are published in the journal Nature Medicine.Molecule activate anti-inflammatory blood cellsThe new blood cells belong to the group of our white blood cells called lymphocytes. The cells express a molecule called FoxA1 that the researchers found is responsible for the cells’ development and suppressive functions.”We knew that some unidentified blood cells were able to inhibit multiple sclerosis-like disease in mice and through gene analysis we found out, that these cells are a subset of our lymphocytes expressing the gene FoxA1. Importantly, when inserting FoxA1 into normal lymphocytes with gene therapy, we could change them to actively regulate inflammation and inhibit multiple sclerosis, explains associated professor Yawei Liu leading the experimental studies.Activating own blood cells for treatment of diseaseFoxA1 expressing lymphocytes were not known until now, and this is the first documentation of their importance in controlling multiple sclerosis. The number of people living with this devastating disease around the world has increased by 10 percent in the past five years to 2.3 million. It affects women twice more than men and no curing treatment exists. …

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Mindfulness-based stress reduction helps lower blood pressure, study finds

Oct. 15, 2013 — Blood pressure is effectively lowered by mindfulness-based stress reduction (MBSR) for patients with borderline high blood pressure or “prehypertension,” according to new research.The finding is reported in the October issue of Psychosomatic Medicine: Journal of Biobehavioral Medicine, the official journal of the American Psychosomatic Society. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.”Our results provide evidence that MBSR, when added to lifestyle modification advice, may be an appropriate complementary treatment for BP in the prehypertensive range,” writes Joel W. Hughes, PhD, of Kent State (Ohio) University and colleagues.Mindfulness Practice Leads to Drop in Blood PressureThe study included 56 women and men diagnosed with prehypertension — blood pressure that was higher than desirable, but not yet so high that antihypertensive drugs would be prescribed. Prehypertension receives increasing attention from doctors because it is associated with a wide range of heart disease and other cardiovascular problems. About 30% of Americans have prehypertension and may be prescribed medications for this condition.One group of patients was assigned to a program of MBSR: eight group sessions of 2½ hours per week. Led by an experienced instructor, the sessions included three main types of mindfulness skills: body scan exercises, sitting meditation, and yoga exercises. Patients were also encouraged to perform mindfulness exercises at home.The other “comparison” group received lifestyle advice plus a muscle-relaxation activity. This “active control” treatment group was not expected to have lasting effects on blood pressure. Blood pressure measurements were compared between groups to determine whether the mindfulness-based intervention reduced blood pressure in this group of people at risk of cardiovascular problems.Patients in the mindfulness-based intervention group had significant reductions in clinic-based blood pressure measurements. …

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Four common genetic variants associated with blood pressure in African-Americans

Sep. 10, 2013 — Case Western Reserve University is part of a landmark study that has discovered four novel gene variations associated with blood pressure. The 19-site meta-analysis, involving nearly 30,000 African-Americans, also found that the set of genetic mutations are also associated with blood pressure across other populations.Epidemiology and biostatistics professor Xiaofeng Zhu, PhD, is co-senior author of the paper, which appears in The American Journal of Human Genetics. The Continental Origins and Genetic Epidemiology Network (COGENT) consortium conducted the research, which is the largest genome-wide association study of blood pressure in individuals of African ancestry. Most gene discovery studies to date have been performed using individuals of European ancestry. Previous genome-wide association studies using samples from individuals of African descent failed to detect any replicable genes associated with blood pressure.”In addition to their disproportionate suffering, hypertension occurs earlier in life for African-Americans compared to individuals of other ancestries,” Zhu explained. “Therefore, it is important to study this population to better understand genetic susceptibility to hypertension.”Zhu and his colleagues also confirmed that previous findings regarding other genes whose presence correlates with increased hypertension risk.”Although it is unknown how the genes regulate blood pressure,” Zhu added, “our findings contribute to better understanding of blood pressure pathways that can lead to future development of drug target for hypertension and may guide therapy for clinical care.”Experts estimate genetic make-up accounts for roughly 40-50 percent of individuals’ susceptibility to hypertension. Other factors associated with the disease include lifestyle, diet, and obesity. Compared to Americans of European-ancestry, African-Americans’ increased hypertension prevalence contributes to a greater risk of stroke, coronary heart disease, and end-stage renal disease.”We anticipated that individuals of African ancestry share similar biology to other populations. However, differences in genomic make-up between African ancestry and other populations have uncovered additional genes affecting blood pressure, in addition to genetic variants that are specific to individuals of African ancestry,” said Nora Franceschini, MD, MPH, nephrologist and research assistant professor of epidemiology at the University of North Carolina at Chapel Hill and first author on the paper.The next phase of study involving the newly discovered gene mutations will investigate their function using human blood samples at the molecular level. …

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Yin-yang effect of sodium and chloride presents salt conundrum

Sep. 8, 2013 — Eat less salt’ is a mantra of our health-conscious times and is seen as an important step in reducing heart disease and hypertension.Too much salt in the diet — and specifically sodium — is widely acknowledged as a major risk factor for high blood pressure however, scientists have found that salt’s other oft-overlooked constituent chloride might also play an important role.A study by researchers at the University of Glasgow has revealed that low chloride levels in the blood is an independent indicator of mortality risk in people with hypertension. The role of chloride in hypertension has received little attention from scientists hitherto.After analysing data from almost 13,000 patients with high blood pressure, followed up over 35 years, the researchers found that low levels of chloride was associated with a higher risk of death and cardiovascular disease.The group with the lowest level of chloride in their blood had a 20% higher mortality rate compared to the other subjects. The results are published in the journal Hypertension.Dr Sandosh Padmanabhan of the Institute of Cardiovascular and Medical Sciences, said: “Sodium is cast as the villain for the central role it plays in increasing the risk of high blood pressure, with chloride little more than a silent extra in the background.”However, our study has put the spotlight on this under-studied chemical to reveal an association between low levels of chloride serum in the blood and a higher mortality rate, and surprisingly this is in the opposite direction to the risks associated with high sodium.”It is likely that chloride plays an important part in the physiology of the body and we need to investigate this further.”Chloride is already measured as part of routine clinical screening and so monitoring of chloride levels could easily be incorporated into clinical practice to identify individuals at high risk.Dr Padmanabhan added: “The results we see from this study are confounding against the knowledge that excess salt is a bad thing, yet higher levels of chloride in the blood seems to be an independent factor that is associated with lower mortality and cardiovascular risk. We seem to have entered a grey area here that requires further investigation.”It is too early to draw any conclusions about relating this finding to salt intake and diet. We need more research to establish exactly what the relationship between chloride and health risk is.”

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Short-term blood sugar control protects the kidney but not the heart in patients with diabetes

Sep. 6, 2013 — An international study has shown that short-term blood sugar control in patients with diabetes has a limited effect on their risk of cardiovascular problems, such as heart disease and stroke.Conventional belief has been that high blood sugar is a major factor in cardiovascular disease. However, this latest research adds to a growing body of evidence that risk of cardiovascular disease in patients with diabetes cannot be managed meaningfully by controlling blood sugar alone.The study, led by researchers at Harvard Medical School, USA, and Hadassah Medical Centre, Israel, supported by other global institutions, including St George’s, University of London, examined the effect of the drug saxagliptin, a new class of medicine used to reduce blood sugar levels, in patients with Type 2 diabetes.There are 280 million people worldwide suffering with Type 2 diabetes, a disease defined by high levels of blood sugar. Diabetes doubles the risk of heart attack and stroke and can reduce life expectancy by up to six years. Recognised long-term effects of the condition include blindness, kidney failure, stroke and heart attack.More than 16,000 patients were studied for over two years to test saxagliptin’s cardiovascular safety and also measure whether it could reduce the risk of cardiovascular and kidney damage.Researchers found that the drug was as safe as existing glucose-controlling medicines. By lowering blood sugar it also successfully reduced the damage diabetes causes to kidney function.Importantly, however, despite control of blood sugar levels researchers found no significant reduction in the risk of major cardiovascular events such as heart attack or stroke.Professor Kausik Ray, the study’s UK national lead from St George’s, University of London, said: “Through this trial we studied the effects of a glucose reducing drug on patients over a two-year period and observed that there was no significant benefit from lowering blood sugar levels with respect to the large blood vessels, which contribute to heart attacks and strokes. We did, though, observe a benefit on smaller vessels that contribute to kidney disease. This trial tells us that cardiovascular risk among diabetes patients must be managed through other mechanisms.”Controlling blood sugar in the short term certainly doesn’t present a very meaningful benefit to a patient at risk of cardiovascular problems, although there could be gains over a much longer period. The most effective way to manage cardiovascular disease is through established interventions such as reducing blood pressure, managing cholesterol and encouraging healthier lifestyles.”It is clear to us now that, in patients with diabetes, there are effective therapies that will reduce their risk of kidney failure and there are separate therapies that will help reduce their risk of cardiovascular problems. More research is needed if we are to find new ways to manage cardiovascular risk in future.”The study, published by the New England Journal of Medicine on Monday 2 September 2013, is the largest diabetes trial ever carried out, conducted at 788 sites across 26 countries. …

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New effective treatment for high blood pressure? Removing tiny organ

Sep. 3, 2013 — Removing one of the tiniest organs in the body has shown to provide effective treatment for high blood pressure. The discovery, made by University of Bristol researchers and published in Nature Communications, could revolutionise treatment of the world’s biggest silent killer.The carotid body — a small nodule (no larger than a rice grain) found on the side of each carotid artery — appears to be a major culprit in the development and regulation of high blood pressure.Researchers, led by Professor Julian Paton, found that by removing the carotid body connection to the brain in rodents with high blood pressure, blood pressure fell and remained low.Professor Paton, from Bristol’s School of Physiology and Pharmacology, said: “We knew that these tiny organs behaved differently in conditions of hypertension but had absolutely no idea that they contributed so massively to the generation of high blood pressure; this is really most exciting.”Normally, the carotid body acts to regulate the amount of oxygen and carbon-dioxide in the blood. They are stimulated when oxygen levels fall in your blood as occurs when you hold your breath. This causes a dramatic increase in breathing and blood pressure until blood oxygen levels are restored. This response comes about through a nervous connection between the carotid body and the brain.Professor Paton commented: “Despite its small size the carotid body has the highest blood flow of any organ in the body. Its influence on blood pressure likely reflects the priority of protecting the brain with enough blood flow.”The team’s work on carotid body research started in the late 1990’s and their recent discovery has since led to a human clinical trial at the Bristol Heart Institute of which the results are expected at the end of the year.Professor Paton added: “This is an extremely proud moment for my research team as it is rare that this type of research can so quickly fuel a human clinical trial. I am delighted that Bristol was chosen as a site for this important trial.”The work was funded by the British Heart Foundation, Cibiem, New York and the National Institutes of Health.

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Blocking molecular pathway reverses pulmonary hypertension in rats

Aug. 28, 2013 — Mark Nicolls and his colleagues discovered that blocking a pathway that causes inflammation could reverse a deadly condition known as pulmonary hypertension in rats.Pulmonary hypertension, a deadly form of high blood pressure that develops in the lungs, may be caused by an inflammation-producing molecular pathway that damages the inner lining of blood vessels, according to a new study by researchers at the Stanford University School of Medicine.The results, published Aug. 28 in Science Translational Medicine, suggest that using medications to block this pathway could lead to the first-known cure for the disease, apart from lung transplantation. The new research could also lead to a better understanding of other diseases involving inflammation of blood vessels, such as coronary artery disease, said Mark Nicolls, MD, senior author of the study and division chief of pulmonary and critical care medicine at Stanford, as well as a staff physician at the Veterans Affairs Palo Alto Health Care System.”We believe that targeting inflammation is an exciting approach to augment current treatments for pulmonary hypertension because it may reverse the underlying cause of the disease,” said Nicolls, who is also director of the Lung Immunology Program and an associate professor of medicine. “We believe this is going to be an approach that helps a large number of patients.”The lead author of the study is Wen Tian, PhD, a research associate in Nicolls’ lab.Pulmonary hypertension, while rare, usually strikes young and middle-aged women, leaving them short of breath and often unable to complete simple daily tasks. The condition can be fatal. The risk is higher for people with certain autoimmune diseases (such as scleroderma or lupus), HIV, congenital heart disease or liver disease. The risk also is higher for those who have used street drugs, such as amphetamines or cocaine, or the diet drug fenphen.About 100,000 people in the United States and Europe have been diagnosed with pulmonary hypertension, but many others are believed to go undiagnosed because the main symptom, shortness of breath, is nonspecific. Until the 1990s, there were no treatments except lung transplantation, which has varying degrees of success.What is known about the disease is that the narrowing of blood vessels in the lungs is caused by a mysterious proliferation of the smooth muscle cells that ring those vessels. As the vessel walls thicken, they become increasingly occluded, choking off blood flow.Blood vessels are elastic tubes that have an outer layer of smooth muscle and an inner layer of endothelial cells. …

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Blocking molecular pathway reverses pulmonary hypertension in rats

Aug. 28, 2013 — Mark Nicolls and his colleagues discovered that blocking a pathway that causes inflammation could reverse a deadly condition known as pulmonary hypertension in rats.Pulmonary hypertension, a deadly form of high blood pressure that develops in the lungs, may be caused by an inflammation-producing molecular pathway that damages the inner lining of blood vessels, according to a new study by researchers at the Stanford University School of Medicine.The results, published Aug. 28 in Science Translational Medicine, suggest that using medications to block this pathway could lead to the first-known cure for the disease, apart from lung transplantation. The new research could also lead to a better understanding of other diseases involving inflammation of blood vessels, such as coronary artery disease, said Mark Nicolls, MD, senior author of the study and division chief of pulmonary and critical care medicine at Stanford, as well as a staff physician at the Veterans Affairs Palo Alto Health Care System.”We believe that targeting inflammation is an exciting approach to augment current treatments for pulmonary hypertension because it may reverse the underlying cause of the disease,” said Nicolls, who is also director of the Lung Immunology Program and an associate professor of medicine. “We believe this is going to be an approach that helps a large number of patients.”The lead author of the study is Wen Tian, PhD, a research associate in Nicolls’ lab.Pulmonary hypertension, while rare, usually strikes young and middle-aged women, leaving them short of breath and often unable to complete simple daily tasks. The condition can be fatal. The risk is higher for people with certain autoimmune diseases (such as scleroderma or lupus), HIV, congenital heart disease or liver disease. The risk also is higher for those who have used street drugs, such as amphetamines or cocaine, or the diet drug fenphen.About 100,000 people in the United States and Europe have been diagnosed with pulmonary hypertension, but many others are believed to go undiagnosed because the main symptom, shortness of breath, is nonspecific. Until the 1990s, there were no treatments except lung transplantation, which has varying degrees of success.What is known about the disease is that the narrowing of blood vessels in the lungs is caused by a mysterious proliferation of the smooth muscle cells that ring those vessels. As the vessel walls thicken, they become increasingly occluded, choking off blood flow.Blood vessels are elastic tubes that have an outer layer of smooth muscle and an inner layer of endothelial cells. …

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Tumor suppressor may actually fuel aggressive leukemia

Aug. 27, 2013 — New research in the Journal of Clinical Investigation suggests that blocking a protein normally credited with suppressing leukemia may be a promising therapeutic strategy for an aggressive form of the disease called acute myeloid leukemia (AML).Researchers from Cincinnati Children’s Hospital Medical Center report their results in a study posted online Aug. 27 by the journal.The protein scientists targeted is a transcription factor known as RUNX1, which also plays an important role in helping regulate the normal development of blood cells. The researchers were surprised to discover in their laboratory tests that RUNX1 was supporting the growth of AML fueled by what are called fusion proteins.”RUNX1 is generally considered a tumor suppressor in myeloid neoplasms, but our study found that inhibiting its activity rather than enhancing it could be a promising therapeutic strategy for AMLs driven by fusion proteins,” said James Mulloy PhD., a researcher in the Division of Experimental Hematology and Cancer Biology at Cincinnati Children’s and lead investigator.AML develops and progresses rapidly in patients, requiring prompt treatment with chemotherapy, radiation or bone marrow transplant. These treatments can be risky or only partially effective depending on the patient as well as the variation and progression of disease. Researchers like Mulloy are searching for improved treatment strategies, including targeted molecular approaches that could potentially be more effective and carry fewer side effects.They tested this finding in a genetic mouse model of AML developed by Mulloy’s laboratory that is driven by fusion proteins and a mixed-lineage leukemic gene called MLL-AF9. The researchers genetically inhibited both RUNX1 and an associated protein called core-binding factor subunit beta (Cbfb). By doing so, the researchers were able to stop the development of leukemia cells, demonstrating the potential viability of RUNX1 as a therapeutic target.Also collaborating on the research was Paul Liu, MD, PhD, at the National Cancer Institute (National Institutes of Health), who developed a small molecule that specifically inhibits RUNX1. Using this inhibitor, the researchers showed that the AML cells were more sensitive than normal blood cells, indicating the inhibitor may be useful in the future as a therapy for patients with AML.The research team continues to test inhibition of RUNX1 in AMLs driven by fusion proteins and in other blood disorders involving RUNX1. Their goal is to see how their findings might eventually lead to potential treatment of human disease.Funding support for the research came, in part, from the National Institutes of Health’s National Center for Research Resources (1UL1RR026314-01), a U.S. …

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Hitting the gym may help men avoid diet-induced erectile dysfunction

Aug. 20, 2013 — Obesity continues to plague the U.S. and now extends to much of the rest of the world. One probable reason for this growing health problem is more people worldwide eating the so-called Western diet, which contains high levels of saturated fat, omega-6 polyunsaturated fatty acids (the type of fat found in vegetable oil), and added sugar. Researchers have long known that this pattern of consumption, as well as the weight gain it often causes, contributes to a wide range of other health problems including erectile dysfunction and heart disease. Other than changing eating patterns, researchers haven’t discovered an effective way to avoid these problems.Searching for a solution, Christopher Wingard and his colleagues at East Carolina University used rats put on a “junk food” diet to test the effects of aerobic exercise. They found that exercise effectively improved both erectile dysfunction and the function of vessels that supply blood to the heart.The article is entitled “Exercise Prevents Western-Diet Associated Erectile Dysfunction and Coronary Artery Endothelial Dysfunction: Response to Acute Apocynin and Sepiapterin Treatment.” It appears in the online edition of the American Journal of Physiology: Regulatory, Integrative, and Comparative Physiology, published by the American Physiological Society.MethodologyFor 12 weeks, the researchers fed a group of rats chow that reflected the Western diet, high in sugar and with nearly half its calories from fat. Another group of rats ate a healthy standard rat chow instead. Half of the animals in each group exercised five days a week, running intervals on a treadmill.At the end of the 12 weeks, anesthetized animals’ erectile function was assessed by electrically stimulating the cavernosal nerve, which causes an increase in penile blood flow and produces an erection. The researchers also examined the rats’ coronary arteries to see how they too responded to agents that would relax them and maintain blood flow to the heart, an indicator of heart health.ResultsThe findings showed that rats who ate the Western diet but stayed sedentary developed erectile dysfunction and poorly relaxing coronary arteries. …

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Longest and largest study of insulin pumps to treat type 1 diabetes in children shows they control blood sugar more effectively and with fewer…

Aug. 18, 2013 — The longest and largest study of the effectiveness of insulin pumps to treat type 1 diabetes in children has shown that the pumps are more effective at controlling blood sugar than insulin injections and cause fewer complications.The research is published in Diabetologia, the journal of the European Association for the Study of Diabetes, and is by Associate Professor Elizabeth Davis, Princess Margaret Hospital for Children, Perth, WA, Australia and colleagues.The increasing use of insulin pump therapy over the last 15 years, particularly in children, has been driven by improvements in pump technology, the availability of insulin analogues, plus factors such as the results of the Diabetes Control and Complications Trial which established the benefits offered by improved blood sugar control. Despite this increased use, the outcomes of pump therapy continue to be debated. However there has been inadequate research into the long term effects of pump therapy in children, with many studies too short in duration or not recruiting enough patients.In this study, a total of 345 patients on pump therapy were matched to controls on injections, with a mean age 11 years (range 2-19 years), with a mean duration of diabetes at the start of pump therapy of 4.1 years (range 6 months to 15.5 years) and a follow up of 3.5 years (range 0-10.5 years). The mean HbA1c reduction (a standard method for measuring blood glucose control) in the pump cohort was 0.6% (6.6 mmol/mol). This improved HbA1c remained significant until seven years of follow up (at which point the numbers in the study were too small to analyse the results with statistical confidence). Both groups started with the same HbA1c and max difference was 1% difference at 6 yrs: 7.6 % in the pump group and 8.6 % in the non-pump group.Pump therapy reduced episodes of severe hypoglycaemia (dangerously low blood glucose) from 14.7 to 7.2 events per 100 patients per year. In contrast, severe hypoglycaemia increased in the non-pump cohort over the same period from 6.8 to 10.2 events per 100 patients per year (probably due to random variation). The rate of admission for diabetic ketoacidosis (a shortage of insulin causing the body to switch to burning fats and producing acidic ketone molecules which cause complications and symptoms, a frequent complication in children with T1DM) was lower in the pump cohort than in the non-pump cohort (2.3 vs 4.7 per 100 patients per year) during follow up.Of the 345 patients on pump therapy, 38 ceased pump therapy during the course of the study; 6 of these were in the first year of treatment, 7 in the second year of treatment, 10 in the third year of treatment with the remainder ceasing treatment after at least 3 sequential years on pump therapy. Some children stop because they become tired of the extra attention needed to manage pump and/or concerned about the physical sight of the pump. …

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High debt could be hazardous to your health

Aug. 15, 2013 — If young people are drowning in debt, their blood pressure may be on the rise and their health could suffer. A new Northwestern Medicine® study has found that high financial debt is associated with higher diastolic blood pressure and poorer self-reported general and mental health in young adults.The study, published in the August issue of Social Science and Medicine, offers a glimpse into the impact debt may have on the health of young Americans.”We now live in a debt-fueled economy,” said Elizabeth Sweet, lead author of the study. “Since the 1980s American household debt has tripled. It’s important to understand the health consequences associated with debt.”Sweet is an assistant professor of medical social sciences at Northwestern University Feinberg School of Medicine and a faculty associate of Cells to Society (C2S): The Center on Social Disparities and Health, at the Institute for Policy Research at Northwestern.Researchers used data from the National Longitudinal Study of Adolescent Health to explore the association between debt and both psychological and general health outcomes in 8,400 young adults, ages 24 to 32 years old.Previous studies have found evidence that debt is associated with adverse psychological health, but this is the first to look at physical health as well.Here are some key findings of the study:Twenty percent of participants reported that they would still be in debt if they liquidated all of their assets (high debt-to-asset-ratio). Higher debt-to-asset ratio was associated with higher perceived stress and depression, worse self-reported general health and higher diastolic blood pressure. Those with higher debt were found to have a 1.3 percent increase (relative to the mean) in diastolic blood pressure — which is clinically significant. A two-point increase in diastolic blood pressure, for example, is associated with a 17 percent higher risk of hypertension and a 15 percent higher risk of stroke.The researchers found that individuals with high compared to low debt reported higher levels of perceived stress (representing an 11.7 percent increase relative to the mean) and higher depressive symptoms (a 13.2 percent increase relative to the mean).”You wouldn’t necessarily expect to see associations between debt and physical health in people who are so young,” Sweet said. “We need to be aware of this association and understand it better. Our study is just a first peek at how debt may impact physical health.”In the study, personal financial debt was measured in two ways. …

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Virus-derived particles target blood cancer

Aug. 13, 2013 — Ottawa researchers have developed unique virus-derived particles that can kill human blood cancer cells in the laboratory and eradicate the disease in mice with few side effects. The study is published in Blood Cancer Journal by co-senior authors Drs. David Conrad and John Bell of the Ottawa Hospital Research Institute (OHRI) and the University of Ottawa (uOttawa).While Dr. Bell and his colleagues have been investigating replicating viruses for the treatment of solid cancers for many years, with very promising results, this is the first major success they have had treating blood cancer (leukemia). It is also the first success they have had using a non-replicating virus-derived particle as opposed to a replicating virus.”Our research indicated that a replicating virus might not be the safest or most effective approach for treating leukemia, so we decided to investigate whether we could make virus-derived particles that no longer replicate but still kill cancer,” said Dr. Conrad, a hematologist conducting research in the Blood and Marrow Transplant Program at The Ottawa Hospital, and currently completing his PhD at OHRI and uOttawa in the Department of Cellular and Molecular Medicine. “We were delighted to see that this novel therapy was very safe at high doses, and worked extremely well in our laboratory leukemia models. We hope to test this in patients in the near future.”The researchers used a specific method and dose of UV light to transform regular replicating viruses into unique particles that could no longer replicate and spread, but could still enter cancer cells efficiently, kill them and stimulate a strong immune response against the cancer. These particles were able to kill multiple forms of leukemia in the laboratory, including samples taken from local patients who had failed all other therapies. …

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Computer model predicts red blood cell flow

Aug. 13, 2013 — Adjacent to the walls of our arterioles, capillaries, and venules — the blood vessels that make up our microcirculation — there exists a peculiar thin layer of clear plasma, devoid of red blood cells. Although it is just a few millionths of a meter thick, that layer is vital. It controls, for example, the speed with which platelets can reach the site of a cut and start the clotting process.”If you destroy this layer, your bleeding time can go way up, by 60 percent or more, which is a real issue in trauma,” said Eric Shaqfeh, the Lester Levi Carter Professor and a professor of chemical engineering and mechanical engineering at Stanford University. Along with his colleagues, Shaqfeh has now created the first simplified computer model of the process that forms that layer — a model that could help to improve the design of artificial platelets and medical treatments for trauma injuries and for blood disorders such as sickle cell anemia and malaria.The model is described in a paper appearing in the journal Physics of Fluids.The thin plasma layer, known as the Fåhræus-Lindqvist layer, is created naturally when blood flows through small vessels. In the microcirculation, the layer forms because red blood cells tend to naturally deform and lift away from the vessel walls. “The reason they don’t just continually move away from the wall and go far away is because, as they move away, then also collide with other red blood cells, which force them back,” Shaqfeh explained. “So the Fåhræus-Lindqvist layer represents a balance between this lift force and collisional forces that exist in the blood.”Because the deformation of red blood cells is a key factor in the Fåhræus-Lindqvist layer, its properties are altered in diseases, such as sickle cell anemia, that affect the shape and rigidity of those cells. The new model, which is a scaled-down version of an earlier numerical model by Shaqfeh and colleagues that provided the first large-scale, quantitative explanation of the formation of the layer, can predict how blood cells with varying shapes, sizes, and properties — including the crescent-shaped cells that are the hallmark of sickle cell anemia — will influence blood flow.The model can also help predict the outcome of — and perfect — treatments for trauma-related injuries. One common thing to do during treatment for trauma injuries is to inject saline, which among other things reduces the hematocrit, the blood fraction of red blood cells. …

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Study shows MicroRNAs can trigger lymphomas

Aug. 8, 2013 — A small group of immune-regulating molecules, when overproduced even moderately, can trigger the blood cancers known as lymphomas, according to a new study led by scientists from The Scripps Research Institute (TSRI).The six “microRNA” molecules were already known to be overproduced in lymphomas and in many other human cancers, but no one had demonstrated that they can be the prime cause of such cancers — until now. The new study also identified the major biological pathways through which these microRNAs ignite and maintain cancerous growth.”We were able to show how this microRNA cluster can be the main driver of cancer, and so we now can start to think about therapies to combat its effects,” said TSRI Assistant Professor Changchun Xiao. Xiao was the senior investigator for the study, which appeared this week in an advance online version of the EMBO Journal, a publication of the European Molecular Biology Organization.’Dimmer Switches’Discovered only in the 1990s, microRNAs are short molecules that work within virtually all animal and plant cells. Typically each one functions as a “dimmer switch” for one or more genes; it binds to the transcripts of those genes and effectively keeps them from being translated into proteins. In this way microRNAs can regulate a wide variety of cellular processes.The focus of the new study was a cluster of six microRNAs known as miR-17~92, encoded by a single gene on chromosome 13. Studies of miR-17~92, including one from Xiao’s lab earlier this year, have shown that it controls various immune-related and developmental processes, depending on the type of cell in which it is expressed.But the miR-17~92 cluster is best known as a suspected cause of cancers, so much so that it has been dubbed “oncomir-1.” Since 2005, scientists have found the cluster to be overproduced in lymphomas, leukemias, brain cancers, breast cancers, prostate cancers and other tumor types. It appears to play an especially prominent role in lymphomas. In a study reported last year, National Cancer Institute researchers found a drastic overexpression of the miR-17~92 cluster in every tumor they sampled from patients with a common type of non-Hodgkin’s lymphoma called Burkitt lymphoma.Researchers have found evidence that this overexpression of miR-17~92 isn’t merely an incidental result of cancerous change in cells; it also works to speed up cancerous growth. “What hasn’t been known is whether miR-17~92 can be the primary trigger of such cancers,” said Xiao.Identifying a Primary Trigger for CancerIn the new study, he and his colleagues demonstrated that it can be. …

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Discovery of novel gene mutations in leukemia patients opens up personalized therapy options

Aug. 2, 2013 — Specific mutations (N676K) in the FLT3 receptor can contribute to the development of acute myeloid leukemia. The FLT3 receptor regulates cell growth, while activating gene mutations promote the uncontrolled proliferation of white blood cells. These findings were reported in the specialist journal Blood by a group of scientists from the Helmholtz Zentrum München and the Hospital of the Ludwig Maximilians University (LMU) in Munich as part of a clinical research collaboration with the German Cancer Consortium (DKTK). The results provide the basis for the development of new leukemia treatments using specific inhibitors, which block growth signals.Share This:Gene mutations often trigger cancer. These changes in the DNA mostly affect the regulators of cellular metabolism or cell growth, which cause cells to degenerate and proliferate rapidly. Many such gene mutations that cause leukemia have been identified.In about one third of patients with acute myeloid leukemia (AML) the malignant cells have a mutation in the growth-regulating FLT3 receptor. As the team of scientists headed by Dr. Philipp Greif and Professor Karsten Spiekermann have now discovered, blood cancer cells from a substantial number of patients in a subgroup of AML (so-called core-binding factor leukemias) also carry mutations in this receptor. Mutations affecting amino-acid position N676 have not been previously detected and may allow a new classification of this form of leukemia, which is characterized by extremely high white blood cell counts. …

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Anemia linked to increased risk of dementia

July 31, 2013 — Anemia, or low levels of red blood cells, may increase the risk of dementia, according to a study published in the July 31, 2013, online issue of Neurology®, the medical journal of the American Academy of Neurology.”Anemia is common in the elderly and occurs in up to 23 percent of adults ages 65 and older,” said study author Kristine Yaffe, MD, with the University of California – San Francisco and a member of the American Academy of Neurology. “The condition has also been linked in studies to an increased risk of early death.”For the study, 2,552 older adults between the ages of 70-79 were tested for anemia and also underwent memory and thinking tests over 11 years. Of those, 393 had anemia at the start of the study. At the end of the study, 445, or about 18 percent of participants, developed dementia.The research found that people who had anemia at the start of the study had a nearly 41 percent higher risk of developing dementia than those who were not anemic. The link remained after considering other factors, such as age, race, sex and education. Of the 393 people with anemia, 89 people, or 23 percent, developed dementia, compared to 366 of the 2,159 people who did not have anemia, or 17 percent.”There are several explanations for why anemia may be linked to dementia. For example, anemia may be a marker for poor health in general, or low oxygen levels resulting from anemia may play a role in the connection. Reductions in oxygen to the brain have been shown to reduce memory and thinking abilities and may contribute to damage to neurons,” said Yaffe.The study was supported by the National Institute on Aging and the American Health Assistance Foundation.

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Cardiovascular risk in type 2 diabetics with dangerously low blood sugar levels

July 30, 2013 — Type 2 diabetics who have severe hypoglycaemia are at higher risk of cardiovascular disease, a new article suggests.Severe hypoglycaemia is a condition where there is an abnormally low content of sugar in the blood. It is often classed as a medical emergency.Severe hypoglycaemia is a potential risk factor for cardiovascular disease in patients with type 2 diabetes and recent clinical trials have failed to demonstrate a beneficial effect of intensive glucose control on overall CVD events.Although observational studies have reported a positive association between severe hypoglycaemia and CVD risk, the association remains controversial. So researchers from Japan, the USA and the Netherlands carried out the first systematic review to assess this association.They analysed the results of six studies involving a study population of 903,510 patients. Information on patients’ characteristics was taken, including: age, gender, duration of diabetes, CVD history, insulin use, BMI and smoking status.In total, 0.6 — 5.8% of participants experienced severe hypoglycaemia from one to five years follow-up. Overall, this added just 1.56% to the total risk of developing cardiovascular disease in the whole population, but the link was consistent with all studies showing a positive correlation.Given this risk, the researchers say avoiding severe hypoglycaemia may be important to prevent CVD and “less stringent glycaemic targets may be considered for type 2 diabetic patients at high risk of hypoglycaemia.”The positive association has been previously explained by having one or more other serious illnesses, but the researchers say this is unlikely to explain this. They suggest that the prevalence of serious illnesses would need to be “unrealistically high” among patients who experienced severe hypoglycaemia and the association between serious illnesses and cardiovascular disease would need to be “extremely strong.”In conclusion, the researchers say that their results suggest “that severe hypoglycaemia is associated with a 2-fold increased risk of CVD.” They say that choices of glucose lowering agents with a low propensity to induce hypoglycaemia, patient education, and self-monitoring of blood glucose can be useful in preventing hypoglycaemia which in turn, “may be important to prevent cardiovascular disease in type 2 diabetes patients.”

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Could sleeping stem cells hold key to treatment of aggressive blood cancer?

July 29, 2013 — Scientists studying an aggressive form of leukemia have discovered that rather than displacing healthy stem cells in the bone marrow as previously believed, the cancer is putting them to sleep to prevent them forming new blood cells.The finding offers the potential that these stem cells could somehow be turned back on, offering a new form of treatment for the condition, called Acute Myeloid Leukemia (AML). The work was led by scientists at Queen Mary, University of London with the support of Cancer Research UK’s London Research Institute.Around 2,500 people are diagnosed with AML in the UK each year, both young and old. Although AML is curable in some the majority die from this disease.Normally, the bone marrow produces haematopoietic stem cells which mature into “adult” blood cells. In people with AML the bone marrow is invaded by leukaemic myeloid cells which aren’t able to develop into normal functioning blood cells.The result is that the body does not have enough red blood cells or platelet cells, which can cause symptoms of anemia, such as tiredness, and increase the risk of excessive bleeding. Patients are also more vulnerable to infection as the white blood cells, which fight bacteria and viruses, are not properly formed.Dr David Taussig, from the Barts Cancer Institute at Queen Mary, University of London, who led the research, said: “The widely accepted explanation has held that AML causes bone marrow failure by depleting the bone marrow of normal haematopoietic stem cells by killing or displacing them.”However, we have found that samples of bone marrow in both mice models and patients with AML contain the same, or more, of these normal stem cells than usual. So the cancer isn’t getting rid of them, instead it appears to be turning them off so they aren’t going on to form healthy blood cells.”If we can find out how the cancer cells are doing this, we can look at exploiting it to find ways to wake these stem cells up. This is very important as, while the cure rate for younger patients can be around 40 per cent, in older patients it is much lower. The treatments we have, such as chemotherapy and bone marrow transplants, just aren’t very successful in this older patient group.”The scientists studied the levels of haematopoietic stem cells (HSC) in the bone marrow of mice transplanted with human AML. They found the numbers of normal mouse HSCs stayed the same, however what did change was that the HSCs were no longer going through the stages of development which finally results in the formation of new blood cells.The findings were confirmed by the analysis of bone marrow from 16 patients with AML.Professor Peter Johnson, Cancer Research UK’s chief clinician, said: “Although major progress has been made in treating AML over the years, there’s still an urgent need for more effective treatments to improve long-term survival. This study takes us an important step forwards in our understanding of what’s going on in the bone marrow of people with AML, an area that we have not known enough about previously, and the challenge now is to turn this understanding into new treatments for patients.”Dr Taussig added: “Usually when the body is stressed, the stem cells become very active. …

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New genetic cause of pulmonary hypertension identified

July 24, 2013 — Columbia University Medical Center (CUMC) scientists have identified new genetic mutations that can cause pulmonary arterial hypertension (PAH), a rare fatal disease characterized by high blood pressure in the lungs. The mutations, found in the gene KCNK3, appear to affect potassium channels in the pulmonary artery, a mechanism not previously linked to the condition. Cell culture studies showed that the mutations’ effects could be reversed with a drug compound known as a phospholipase inhibitor.The study was published today in the online edition of the New England Journal of Medicine.”The most exciting thing about our study is not that we’ve identified a new gene involved in pulmonary hypertension, but that we’ve found a drug that can ‘rescue’ some mutations,” said co-senior author Wendy K. Chung, MD, PhD, associate professor of pediatrics and medicine at CUMC. “In genetics, it’s common to identify a gene that is the source of a disease. However, it’s relatively rare to find potential treatments for genetic diseases.”PAH is a progressive disorder characterized by abnormally high blood pressure in the pulmonary artery, which reduces blood flow from the right side of the heart to the lungs. The heart can compensate by pumping harder, but over time this can weaken the heart muscle and lead to right-sided heart failure. Common symptoms of PAH include shortness of breath, dizziness, and fainting. About 1,000 new cases are diagnosed in the United States each year. The disorder is twice as common in females as in males. …

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