Category: Health

{Malaria caused by Plasmodium parasites is a life-threatening infectious disease that kills at least half a million people annually while causing over 200 million new infections. In some cases, complications can quickly develop such as cerebral malaria, respiratory distress and severe anemia, often leading to death. The majority of patients recover from disease, however, there is increasing evidence to suggest that survivors experience long-term ‘hidden’ pathologies due to infection that are as yet poorly defined.}

Now, the Laboratory of Malaria Immunology Team at the Immunology Frontier Research Center (IFReC), Osaka University, headed by Professor Cevayir COBAN, have used mouse malaria models to show that robust immune activation and invasion of parasite by-products into the bone marrow during and after malaria infection leads to an adverse balance in bone homeostasis -a process usually tightly controlled- by bone forming osteoblasts and bone resorbing osteoclasts.

“Even after a one time malaria infection (it does not matter if the disease is completely cured or chronic low level infection continues), substantial chronic bone loss occurs,” Dr. Coban, corresponding author of the study, says. Michelle Lee, a PhD candidate and the first author of the study explains, “We found that Plasmodium products continuously accumulate in the bone marrow niche which turns the bone noticeably black in color, and results in it being “eaten-up” by bone resorbing cells known as osteoclasts, eventually disrupting bone homeostasis.” These products, including the major malarial by-product hemozoin, malarial proteins and as yet undefined virulence factors, induce MyD88-dependent inflammatory responses in osteoclast and osteoblast precursors, leading to increased RANKL expression (a key molecule inducing osteoclast differentiation), and over-stimulation of osteoclastogenesis favoring bone resorption.” The Coban Team infected mice with a mutant Plasmodium parasite producing less by-products such as hemozoin, and discovered in this case bone loss did not occur, thereby confirming their findings.

Dr. Coban explains, “Although chronic inflammatory conditions are known to facilitate bone disorders, our study -for the first time- shows that malaria can do the same thing, with hallmark “signatures” left in the bone tissue, a very unique feature of malaria infection. One may think that the infection has been completely cured by anti-malarial treatment, and be feeling fully recovered, however, sustained long-term accumulation of parasite by-products leave the bone in a state of chronic inflammation, leading to long term bone loss. This is particularly worrisome in the young of age, where it may cause growth problems and osteoporotic, fragile bones.”

Importantly, the study shows that there is a simple way to reverse the side effects of malaria infection on bone. Oral supplementation with alfacalcidol, a vitamin D3 analog, could completely prevent bone loss. Therefore, anti-malarials coupled with bone therapy may be beneficial in improving bone health in malaria-infected individuals.

Source:Science Daily

{A single treatment giving life-long protection from severe allergies such as asthma could be made possible by immunology research at The University of Queensland.}

A team led by Associate Professor Ray Steptoe at the UQ Diamantina Institute has been able to ‘turn-off’ the immune response which causes allergic reaction in animals.

“When someone has an allergy or asthma flare-up, the symptoms they experience results from immune cells reacting to protein in the allergen,” Professor Steptoe said.

“The challenge in asthma and allergies is that these immune cells, known as T-cells, develop a form of immune ‘memory’ and become very resistant to treatments.

“We have now been able ‘wipe’ the memory of these T-cells in animals with gene therapy, de-sensitising the immune system so that it tolerates the protein.

“Our work used an experimental asthma allergen, but this research could be applied to treat those who have severe allergies to peanuts, bee venom, shell fish and other substances.”

Dr Steptoe said the findings would be subject to further pre-clinical investigation, with the next step being to replicate results using human cells in the laboratory.”

“We take blood stem cells, insert a gene which regulates the allergen protein and we put that into the recipient.

“Those engineered cells produce new blood cells that express the protein and target specific immune cells, ‘turning off’ the allergic response.”

Dr Steptoe said the eventual goal would be a single injected gene therapy, replacing short-term treatments that target allergy symptoms with varying degrees of effectiveness.

“We haven’t quite got it to the point where it’s as simple as getting a flu jab, so we are working on making it simpler and safer so it could be used across a wide cross-section of affected individuals,” Dr Steptoe said.

“At the moment, the target population might be those individuals who have severe asthma or potentially lethal food allergies.”

Dr Steptoe’s research has been funded by the Asthma Foundation and the National Health and Medical Research Council.

Asthma Foundation of Queensland and New South Wales Chief Executive Officer Dr Peter Anderson said more than two million Australians have asthma, and current statistics show that more than half of those are regularly burdened with symptoms of the disease.

“Even though there are effective treatments available for the vast majority, patients face a number of obstacles and challenges in their self-management practices,” Dr Anderson said.

“The Foundation welcomes the findings of this research and looks forward to a day in the future when a safe one-off treatment may be available that has the potential to eliminate any experience of asthma in vulnerable patients.”

Source:Science Daily

{Using evidence found in baby teeth, researchers from The Senator Frank R. Lautenberg Environmental Health Sciences Laboratory and The Seaver Autism Center for Research and Treatment at Mount Sinai found that differences in the uptake of multiple toxic and essential elements over the second and third trimesters and early postnatal periods are associated with the risk of developing autism spectrum disorders (ASD), according to a study published June 1 in the journal Nature Communications.}

The critical developmental windows for the observed discrepancies varied for each element, suggesting that systemic dysregulation of environmental pollutants and dietary elements may serve an important role in ASD. In addition to identifying specific environmental factors that influence risk, the study also pinpointed developmental time periods when elemental dysregulation poses the biggest risk for autism later in life.

According to the U.S. Centers for Disease Control and Prevention, ASD occurs in 1 of every 68 children in the United States. The exact causes are unknown, but previous research indicates that both environmental and genetic causes are likely involved. While the genetic component has been intensively studied, specific environmental factors and the stages of life when such exposures may have the biggest impact on the risk of developing autism are poorly understood. Previous research indicates that fetal and early childhood exposure to toxic metals and deficiencies of nutritional elements are linked with several adverse developmental outcomes, including intellectual disability and language, attentional, and behavioral problems.

“We found significant divergences in metal uptake between ASD-affected children and their healthy siblings, but only during discrete developmental periods,” said Manish Arora, PhD, BDS, MPH, Director of Exposure Biology at the Senator Frank Lautenberg Environmental Health Sciences Laboratory at Mount Sinai and Vice Chair and Associate Professor in the Department of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai. “Specifically, the siblings with ASD had higher uptake of the neurotoxin lead, and reduced uptake of the essential elements manganese and zinc, during late pregnancy and the first few months after birth, as evidenced through analysis of their baby teeth. Furthermore, metal levels at three months after birth were shown to be predictive of the severity of ASD eight to ten years later in life.”

To determine the effects that the timing, amount, and subsequent absorption of toxins and nutrients have on ASD, Mount Sinai researchers used validated tooth-matrix biomarkers to analyze baby teeth collected from pairs of identical and non-identical twins, of which at least one had a diagnosis of ASD. They also analyzed teeth from pairs of normally developing twins that served as the study control group. During fetal and childhood development, a new tooth layer is formed every week or so, leaving an “imprint” of the micro chemical composition from each unique layer, which provides a chronological record of exposure. The team at the Lautenberg Laboratory used lasers to reconstruct these past exposures along incremental markings, similar to using growth rings on a tree to determine the tree’s growth history.

“Our data shows a potential pathway for interplay between genes and the environment,” says Abraham Reichenberg, PhD, Professor of Psychiatry and Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai. “Our findings underscore the importance of a collaborative effort between geneticists and environmental researchers for future investigations into the relationship between metal exposure and ASD to help us uncover the root causes of autism, and support the development of effective interventions and therapies.”

Additional studies are needed to determine whether the discrepancies in the amount of certain metals and nutrients are due to differences in how much a fetus or child is exposed to them or because of a genetic difference in how a child takes in, processes, and breaks down these metals and nutrients.

Source:Science Daily

{Cellphones are addictive, and important too. Addictive because you have all the cool apps and games you love to have fun with, and important because you have to stay in touch, I mean, you never really know when that life- changing call will come in, so, you need to carry it around and keep it as close to you as possible, even if it means taking it to bed with you. But as ‘harmless’ as it may seem, going to bed with your mobile phone isn’t quite good for you, and that’s because of the following reasons…}

{{Defeats the purpose of going to bed }}

Unless you’re getting in your bed to sit and not sleep, then, there’s nothing wrong with taking your phone with you, but if the intention is to get some sleep, then, there’s absolutely no point taking your phone because you’ll probably end up not sleeping at all. Consider the notifications that will keep pouring in, the calls and the temptation to try that game one more time. Don’t forget health experts advise that you get at least 8hrs sleep every night to stay in good shape.

{{Your eyes can be endangered }}

Over using your phone at night can expose your eyes to vision problems. This is due to the fact that most smart phones today emit blue light which is potentially dangerous if stared into for long. It can lead to dryness of the eyes and blurred vision.

{{Nomophobia }}

Nomophobia is the fear of being without a mobile phone. This happens when you’re addicted to using one, and it can lead to unnecessary anxiety. If you fall asleep while using your phone, chances are you’ll wake up in the middle of the night anxiously looking for it, and in the end you end up disrupting your sleep.

{{It can ruin your relationship }}

For most couples, bedtime is ‘us’ time. It’s a time for a couple to catch up on stuff they might have missed in each other’s lives during the day. You can imagine how awful that would be if you go to bed with your phone. You’ll be distracted, and your partner would be frustrated with you.

{{Exposure to radiation }}

You may not know this, but smartphones usually release a form of non-ionizing electromagnetic radiation, which can be absorbed if it is too near your body. However, the risk is reduced when the phone is turned off.

Source:Science Daily

{A new study in Biological Psychiatry may pave the way for treating alcohol addiction by reducing motivation to drink, rather than by altering the effects of alcohol itself. Led by Drs. Kasia Radwanska and Leszek Kaczmarek of the Nencki Institute, Warsaw, Poland, the study reports a new mechanism behind alcohol seeking behavior.}

When people think about drugs to treat alcoholism, their first thought is usually a drug that stimulates or blocks a receptor for a chemical messenger. However, the new study highlights a process that changes brain activity by altering the network of proteins that surrounds nerve cells. This network of proteins, called the extracellular matrix, provides active support for the development and activity of nerve cells. The functions of the matrix are regulated, in part, by enzymes that break down matrix proteins; one of these enzymes is matrix metalloproteinase-9 (MMP-9).

In the study, while mice had free access to alcohol to establish addiction-like behavior, those missing the enzyme MMP-9 (MMP-9 KO) drank just as much as normal mice. However, first author Dr. Marzena Stefaniuk and colleagues found that MMP-9 KO mice were less motivated to obtain alcohol when its access was restricted, and less persistent to seek alcohol during withdrawal — behaviors normally characteristic of addiction. The researchers were able to restore the impaired motivation by replacing MMP-9 in the central amygdala, a part of the brain’s emotional center that has also been implicated in alcohol dependence.

“Interestingly, in human alcoholics, the MMP-9 gene polymorphism that leads to a higher MMP-9 production correlates with greater motivation to drink alcohol,” said Dr. Kaczmarek, referring to their analysis of 167 alcohol-addicted males compared with 199 control males, also included in the new study. Using a clinical assessment of alcoholism behavior, the researchers found that addicted people with a T allele in the MMP-9 gene continued to drink alcohol despite the negative consequences more frequently than patients with a C allele. The findings further support the role of MMP-9 in motivation for alcohol.

“Matrix metalloproteinases play critical roles in brain function and disease that have only recently received intensive study,” said Dr. John Krystal, Editor of Biological Psychiatry. “The exciting study by Stefaniuk and colleagues implicates them in alcohol use disorders, but they are likely to play roles quite broadly in psychiatric disorders. It will be important to determine whether these proteins may be targeted therapeutically.”

In previous studies, MMP-9 has been demonstrated to be mandatory in the central amygdala for formation of appetitive memory traces via synaptic plasticity — the structural and physiological alteration of synapses, the connections that facilitate communication between neurons. Indeed, the loss of MMP-9 in mice impaired structural and physiological alcohol-related alterations in the central amygdala, leading the authors to suggest MMP-9-dependent synaptic plasticity in this brain region as a new mechanism behind alcohol craving.

“In aggregate, these findings point to MMP-9 as a novel therapeutic target in fighting alcohol addiction,” said Kaczmarek.

Source:Science Daily

{Researchers from Monash University have developed a new drug delivery strategy able to block pain within the nerve cells, in what could be a major development of an immediate and long lasting treatment for pain.}

More than 100 million Americans suffer from chronic pain and this figure is expected to grow, driven by the increased life expectancy, increasing incidence of diabetes and cancer, combined with better survival rates, often leaving patients with severe and poorly treated pain. The global market for nerve pain treatments is over US$600 billion and yet current pain therapies are not completely effective and often suffer from unwanted side effects.

Research published in the journal, Science Translational Medicine, reveals how a target protein, long known to be associated with both chronic and acute pain, works within the nerve cell. This protein is the NK1 receptor, the receptor of the neuropeptide substance P, which mediates pain transmission. Because of its association with pain and other diseases of the nervous system, many drug development attempts have focused on inhibiting this receptor, but the efficacy of these treatments has been very limited. This new work shows that such ineffectiveness could be in part because the treatments targeted the protein on the surface of the nerve cell.

Dr Michelle Halls and Dr Meritxell Canals from the Monash Institute of Pharmaceutical Sciences (MIPS) and the ARC Centre for Excellence in Bio-Nano Science (CBNS) at Monash University, have worked with Professor Nigel Bunnett, previously at Monash and now at Columbia University in the US, and Professor Chris Porter from MIPS and CBNS.

Together they have found that the NK-1 receptor controls pain once it is inside the cell — so drugs that merely block it when it is on the surface of the cell have little efficacy. Instead, this new research shows that, in animal models, if the NK-1 receptor is blocked once it enters the nerve cell, it is possible to suppress pain more effectively.

Dr Halls said that the new strategy of “targeting receptors inside the cell represents a new frontier in drug delivery and a novel therapeutic strategy for dealing with pain.”

Working with a multidisciplinary team of cell biologists, pharmacologists, physiologists and drug delivery experts, the researchers developed drugs that specifically target NK-1 receptors within the nerve cell. Animal studies showed that using the drugs — which have an engineered lipid attachment that targets the drug to the NK-1 receptor inside the cell, could block pain for extended periods in several animal models.

Dr Canals said: “This is a proof-of-concept study that shows that we can re-engineer current pain drugs and make them more effective. The challenge is now to translate the technology into human clinical trials. This is a complex and challenging path — but the ultimate benefits to patients with nerve pain are potentially highly significant.”

Source:Police

{Epigenetic changes are chemical modifications that turn our genes off or on. In a new study from Uppsala University, researchers show that tea consumption in women leads to epigenetic changes in genes that are known to interact with cancer and estrogen metabolism. The results are published in the journal Human Molecular Genetics.}

It is well known that our environment and lifestyle factors, such as food choices, smoking and exposure to chemicals, can lead to epigenetic changes. In the current study, researchers from Uppsala University in collaboration with research groups around Europe, investigated if coffee and tea consumption may lead to epigenetic changes. Previous studies have suggested that both coffee and tea play an important role in modulating disease-risk in humans by suppressing tumour progression, decreasing inflammation and influencing estrogen metabolism, mechanisms that may be mediated by epigenetic changes.

The results show that there are epigenetic changes in women consuming tea, but not in men. Interestingly, many of these epigenetic changes were found in genes involved in cancer and estrogen metabolism. “Previous studies have shown that tea consumption reduces estrogen levels which highlights a potential difference between the biological response to tea in men and women. Women also drink higher amounts of tea compared to men, which increases our power to find association in women,” says Weronica Ek, researcher at the Department of Immunology, Genetics and Pathology, who led the study. The study did not find any epigenetic changes in individuals drinking coffee.

Results from this study highlight the role of pharmacologically active components in tea being involved in cancer and estrogen metabolism, which can reflect that health effects related to tea consumption might be due to epigenetic changes. However, this study does not show if it is healthy or not to drink tea and further research is needed to understand how epigenetic changes found in this study affects our health. It has previously been demonstrated that tea catechins lead to epigenetic changes in vitro and in cultured cancer cells, arguing that some of the health effects of tea may be mediated by epigenetics.

Source:Science Daily

{The quest to develop a cure for HIV has long been plagued by a seemingly simple question: How do doctors determine if someone is cured? The virus has a knack for lying dormant in immune cells at levels undetectable to all but the most expensive and time-consuming tests.}

Scientists at the University of Pittsburgh’s Graduate School of Public Health announced in Nature Medicine that they’ve created a test sensitive enough to detect “hidden” HIV, and yet is faster, less labor-intensive and less expensive than the current “gold standard” test.

The new Pitt test also revealed that the amount of virus lurking dormant in people who appear to be nearly cured of HIV is about 70-fold larger than previous estimates.

“Globally there are substantial efforts to cure people of HIV by finding ways to eradicate this latent reservoir of virus that stubbornly persists in patients, despite our best therapies,” said senior author Phalguni Gupta, Ph.D., professor and vice chair of Pitt Public Health’s Department of Infectious Diseases and Microbiology. “But those efforts aren’t going to progress if we don’t have tests that are sensitive and practical enough to tell doctors if someone is truly cured.”

HIV spreads by infecting CD4+ T cells, which are a type of white blood cell that plays a major role in protecting the body from infection. Antiretroviral therapies to treat HIV have advanced to the point that people with HIV can have the virus so well-controlled that they could have as little as one infectious virus per million CD4+ T cells.

However, the majority of HIV DNA integrated into these cells is defective, meaning it wouldn’t cause infection anyway. Once HIV therapy is working, it becomes critical to determine if the HIV DNA being detected by a test could actually create more virus and cause the person to relapse if therapy is stopped. Therefore, the test must be able to show that the virus it detects can replicate — typically by growing the virus from the sample.

To date, the best test available to do this is called a “quantitative viral outgrowth assay,” or Q-VOA. This test has many drawbacks: It may provide only a minimal estimate of the size of the latent HIV reservoir; requires a large volume of blood; and is labor-intensive, time-consuming and expensive.

Gupta’s team developed a test that they call TZA. It works by detecting a gene that is turned on only when replicating HIV is present, thereby flagging the virus for technicians to quantify.

The TZA test produces results in one week compared to the two weeks needed using the Q-VOA, and at a third of the cost. It also requires a much smaller volume of blood and is less labor-intensive.

“Using this test, we demonstrated that asymptomatic patients on antiretroviral therapy carry a much larger HIV reservoir than previous estimates — as much as 70 times what the Q-VOA test was detecting,” said Gupta. “Because these tests have different ways to measure HIV that is capable of replicating, it is likely beneficial to have both available as scientists strive toward a cure.”

Because of its low cell requirement, the TZA also may be useful for quantification of replication-competent HIV-1 in the pediatric population, as well as in the lymph nodes and tissues where the virus persists.

Source:Science Daily