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News - Week 14 - 2009

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MSU researcher links cholesterol crystals to cardiovascular attacks

For the first time ever, a Michigan State University researcher has shown cholesterol crystals can disrupt plaque in a patient’s cardiovascular system, causing a heart attack or stroke. The findings by a team led by George Abela, chief of the cardiology division in MSU’s College of Human Medicine, could dramatically shift the way doctors and researchers approach cardiovascular attacks. Abela’s findings appear in the April issue of the American Journal of Cardiology. “Any time there is something completely new or unique in medical research, it is met with healthy skepticism,” said Abela, who has been working with cholesterol crystals since 2001. “But we have found something that can help dramatically change how we treat heart disease.” What Abela and his team found is that as cholesterol builds up along the wall of an artery, it crystallizes from a liquid to a solid state and then expands. “As the cholesterol crystallizes, two things can happen,” Abela said. “If it’s a big pool of cholesterol, it will expand, causing the ‘cap’ of the deposit to tear off in the arterial wall. Or the crystals, which are sharp, needle-like structures, poke their way through the cap covering the cholesterol deposit, like nails through wood.”The crystals then work their way into the bloodstream. It is the presence of this material, as well as damage to an artery, that disrupts plaque and puts the body’s natural defense mechanism – clotting – into action, which can lead to dangerous, if not fatal, clots. Abela and his team studied coronary arteries and carotid plaques from patients who died of cardiovascular attacks. When comparing their findings against a control group, they found evidence of cholesterol crystals disrupting plaque.The breakthrough in discovering the crystals’ impact came after Abela and colleagues found a new way to preserve tissue after an autopsy, using a vacuum dry method instead of an alcohol solution. The previous method would dissolve the crystals and prevent researchers and doctors from seeing the impact.

Mayo Study Shows Simple Finger Device May Help Predict Future Heart Events, Such as Heart Attack

Results of a Mayo Clinic study show that a simple, noninvasive finger sensor test is "highly predictive" of a major cardiac event, such as a heart attack or stroke, for people who are considered at low or moderate risk, according to researchers. The noninvasive finger test device, called the EndoPAT by Itamar Medical, measures the health of endothelial cells by measuring blood flow. Endothelial cells line the blood vessels and regulate normal blood flow. Research has shown that if the cells don't function properly — a condition called endothelial dysfunction — it can set the stage for atherosclerosis (hardening of the arteries) and lead to major cardiovascular health problems. Previously, there was no simple test for endothelium function, says Amir Lerman, M.D., a cardiologist at Mayo Clinic and the senior author of the study.

Michael Pollan: The omnivore's next dilemma

New study suggests Rx estrogen delivery through the skin may show safety benefits as opposed to oral delivery

Transdermal delivery of estrogen therapy available by prescription "seems not to alter" the risk of venous thromboembolism (VTE), or blood clotting, in postmenopausal patients when compared to oral delivery, a new study suggests. The study was conducted by researchers at NYU Langone Medical Center and was published in the latest issue of Menopause: The Journal of the North American Menopause Society.Prescription transdermal estrogen therapy is bioidentical to estrogen produced by a woman's ovaries before menopause and delivered through the skin. Transdermal estrogen is available in a variety of formulations which have been quality controlled and approved safe and effective by the United States Food and Drug Administration (FDA). The team at NYU Langone sought to determine the effects of delivery of estrogen therapy on postmenopausal women. Blood obtained from 84 postmenopausal women was tested for clotting activity before and after administration of oral or transdermal estrogen for a period of eight weeks. Women with borderline clotting issues showed "a significant acceleration" of clotting after oral estrogen therapy, but no significant change after transdermal estrogen therapy. "Venous thromboembolic complications or blood clots represent an established risk factor of estrogen therapy, and evidence is now mounting that the route of estrogen administration influences this risk," said researcher Lila Nachtigall, M.D., Director of the Women's Wellness Program at NYU. "These new data on the safety of transdermal HT delivery may prove to be useful information for postmenopausal women deciding whether to take estrogen therapy and whether to take it orally or through the skin."

Scripps scientists find structure of a protein that makes cancer cells resistant to chemotherapy

A research team at the Scripps Research Institute has obtained the first glimpse of a protein that keeps certain substances, including many drugs, out of cells. The protein, called P-glycoprotein or P-gp for short, is one of the main reasons cancer cells are resistant to chemotherapy drugs. Understanding its structure may help scientists design more effective drugs.The new research was described in the March 27, 2009, issue of the journal Science. "This structure is an important advance and we hope it is just the beginning of more breakthroughs for us," says the study's senior author Geoffrey Chang, an associate professor at Scripps Research. "The structure is a nice tool for understanding how drugs are transported out of cells by P-gp and for designing drugs to evade P-gp preventing drug resistance. It's very exciting." P-gp, a protein first identified in 1976, sits in the membrane that surrounds human cells, including those in the gut, intestine, kidney, and brain, where it functions as a gate keeper, shooing out potentially harmful agents. Problematically, P-gp not only transports substances that are harmful out of the cell, but also drugs targeted to cancer cells and HIV-infected cells, as well as some therapeutics aimed at alleviating psychiatric conditions. "We've long known that P-glycoprotein plays a key role in multidrug resistance in cancer patients, and this work helps us understand how the protein can act on such a wide range of compounds," said Jean Chin, Ph.D., of the National Institutes of Health's (NIH) National Institute of General Medical Sciences (NIGMS), which partially supported the work. "In the future, scientists may be able to use these crystal structures to design chemicals that block P-glycoprotein's activity and restore sensitivity to chemotherapeutic agents."

MBL researchers discover a mechanism of neurodegeneration in Alzheimer's disease

Tiny, toxic protein particles severely disrupt neurotransmission and inhibit delivery of key proteins in Alzheimer's disease, two separate studies by Marine Biological Laboratory (MBL) researchers have found.
The particles are minute clumps of amyloid beta, which has long been known to accumulate and form plaques in the brain of Alzheimer's patients. "These small particles that haven't aggregated into plaques—these are increasingly being seen as the really toxic species of amyloid beta," says Scott Brady of University of Illinois College of Medicine, who has been an MBL investigator since 1982. Brady and his colleagues found that these particles inhibit neurons from communicating with each other and with other target cells in the body. "The disease symptoms for Alzheimer's are associated not with the death of the neurons – that is a very late event – but with the loss of functional connections. It's when the neuron is no longer talking to its targets that you start to get the memory deficits and dementia associated with the disease," Brady says.
The amyloid beta particles activate an enzyme, CK2, which in turn disrupts the "fast axonal transport" system inside the neuron, Brady found. This transport system has motor proteins that move various kinds of cargo (including neurotransmitters and the associated protein machinery for their release) from place to place in the neuron on microtubule tracks. Brady's findings are complemented by a new study by Rudolfo Llinás of New York University School of Medicine. Brady and Llinás both conduct neuroscience research at the MBL using the giant nerve cell of the Woods Hole squid, Loligo paeleii, as a model system.

Vitamin B and Folic Acid Supplements Prevent Migraines

Increased intake of folic acid and other B vitamins may reduce the frequency and severity of migraine attacks, according to a study conducted by researchers from the Genomics Research Center at Australia's Griffith University.

URI scientists reveal mechanism that regulates cancer-causing gene

Two University of Rhode Island scientists have revealed how a cancer causing protein is regulated by reactive oxygen species (ROS) -- a type of stress signal. Their findings provide new insight into how this protein normally behaves in human cells and may help in the design of drugs targeting specific cancers. Doctoral student David J. Kemble and Professor Gongqin Sun in the URI Department of Cell and Molecular Biology are the first to provide a biochemical mechanism describing how certain protein tyrosine kinases sense and respond to oxidation. This sensing system was found to uniquely apply to two families of proteins implicated in numerous cancers: the Src and Fibroblast Growth Factor Receptor families of tyrosine kinases. Their results were published online March 9 in the Proceedings of the National Academy of Sciences. Src was the first enzyme identified as a cancer-causing gene in the early 1900's. For years scientists have been studying how the enzymes are expressed in cancer cells – what do they do and what controls them. According to Kemble and Sun, Src is a master regulator of cell function, controlling cell metabolism, division, and death. In normal cells, the function of Src is turned off, and it is turned on only when certain stimulatory signals activate it. When the regulatory mechanisms that control Src activity are disrupted, Src may be turned on all the time, which turns the host cell into a cancer cell. Thus, it is crucial to understand how Src function is controlled.

Hormone-mimics in plastic water bottles - just the tip of the iceberg?

Plastic packaging is not without its downsides, and if you thought mineral water was ‘clean’, it may be time to think again. According to Martin Wagner and Jörg Oehlmann from the Department of Aquatic Ecotoxicology at the Goethe University in Frankfurt am Main, Germany, plastic mineral water bottles contaminate drinking water with estrogenic chemicals. In an analysis1 of commercially available mineral waters, the researchers found evidence of estrogenic compounds leaching out of the plastic packaging into the water. What’s more, these chemicals are potent in vivo and result in an increased development of embryos in the New Zealand mud snail. These findings, which show for the first time that substances leaching out of plastic food packaging materials act as functional estrogens, are published in Springer’s journal Environmental Science and Pollution Research.

Questioning Why Healthcare Information Technology Manufacturers Are Free of All Liability When Their Products Can Result in Medical Errors

Even when their products are implicated in harm to patients, manufacturers of healthcare information technology (HIT) currently enjoy wide contractual and legal protection that renders them virtually “liability-free,” writes Ross Koppel, Ph.D., of the University of Pennsylvania School of Medicine, in the March 25th issue of the Journal of the American Medical Association. The current system needs to be changed so that all liability does not rest entirely with physicians, nurses, hospitals, and clinics, even when these users of faulty HIT scrupulously follow vendor instructions, according to Dr. Koppel’s piece, co-authored with David Kreda, a software designer. The HIT industry avoids liability by relying on a legal doctrine known as “learned intermediaries” that holds physicians, nurses, pharmacists, and healthcare technicians responsible for HIT errors because are presumed to be able to identify—and correct— medical mistakes generated by software faults. “HIT vendors claim that, because they cannot practice medicine, clinicians should be accountable for identifying errors resulting from faulty software or hardware,” said Koppel. “But errors or lack of clarity in HIT software can create serious, even deadly, risks to patients that clinicians cannot foresee.”

Missing or mutated "clock" gene linked to vascular disease

The circadian clocks that set the rhythmic motion of our bodies for wakeful days and sleepy nights can also set us up for vascular disease when broken, Medical College of Georgia researchers say. Mice with mutated or missing "clock" genes are prone to thick, inflexible blood vessels with narrow passageways, unhealthy changes typically associated with risk factors such as smoking, high blood pressure and cholesterol, according to research in this week's issue of Circulation. "Having a bad or broken clock seems to promote vascular disease," says Dr. Daniel Rudic, vascular biologist in the MCG Schools of Medicine and Graduate Studies and the study's corresponding author.

Changes in gene may stunt lung development in children

Mutations in a gene may cause poor lung development in children, making them more vulnerable to diseases such as chronic obstructive pulmonary disease (COPD) later in life, say researchers at the University of Pittsburgh Graduate School of Public Health and the German Research Center for Environmental Health. Their study, published online in Physiological Genomics, measured expression levels of the gene and its variants in both mouse lungs and children ages 9 to 11. Study authors, led by George Leikauf, Ph.D., professor of occupational and environmental health at the University of Pittsburgh Graduate School of Public Health, and Holger Schulz, M.D., professor of medicine at the Institute of Lung Biology and Disease, German Research Center for Environmental Health, Munich, focused on a gene called superoxide dismutase 3 (SOD3), previously shown to protect the lungs from the effects of asbestos and oxidative stress. "People lose lung function as they age, so it's important to identify possible genetic targets that control healthy development of the lungs during childhood," said Dr. Leikauf. Drs. Leikauf, Schulz and colleagues compared SOD3 expression levels in strains of mice with poor lung function to one with more efficient airways and lungs two times the size. As with people, the lungs of mice fully form as they mature to adulthood. The better-functioning strain maintained higher levels of SOD3 – levels in these mice were four times higher at the final stage of lung development. They also found the presence of single nucleotide polymorphisms, or SNPs, variations in DNA sequences, in SOD3 that were linked to lung function in mice.

DNA repair mechanisms relocate in response to stress

Like doctors making house calls, some DNA repair enzymes can relocate to the part of the cell that needs their help, a collaborative team of scientists at Emory University School of Medicine has found. The signal that prompts relocation is oxidative stress, an imbalance of cellular metabolism connected with several human diseases. The study integrated the expertise of three Emory groups and resulted in a new level of understanding of the cell's response to genetic damage. The finding could lead to new targets for anti-cancer drugs that interfere with DNA repair, says Paul Doetsch, PhD, professor of biochemistry, radiation oncology, and hematology and oncology at Emory University School of Medicine. The results were published in the February 1 issue of Molecular and Cellular Biology. The journal's editors chose an image of yeast cells with fluorescent DNA repair enzymes for the cover. "DNA damage and oxidative stress are very closely related," Doetsch says. "For example, the way radiation inflicts most of its damage on DNA is through oxidative stress. The more we know about how cells respond to oxidative stress, the more chances there could be to influence those responses for diagnostic or therapeutic purposes." The DNA inside cells is continually under assault by heat, radiation and oxygen. Cells have an extensive set of repair enzymes that comb through DNA, continually excising and re-copying damaged segments. To complicate matters, mitochondria (cells' miniature power plants) have their own DNA.

New Study Finds Financial Advice Causes "Off-Loading" in the Brain

A study using functional magnetic resonance imaging (fMRI) shows that expert advice may shut down areas of the brain responsible for decision-making processes, particularly when individuals are trying to evaluate a situation where risk is involved. The study was published in the March 2009 issue of the Public Library of Science (PLOS One). During times of uncertainty such as an economic recession, many people feel unqualified to sort out the implications of their financial decisions. Often they will seek the advice of a consultant on what choices to make. In a study led by Gregory Berns, MD, PhD, professor of neuroeconomics and psychiatry at Emory University School of Medicine, researchers investigated the neural mechanisms through which advice is integrated into the financial decision making process. "While the field of neuroeconomics has made progress in understanding the neurobiological basis of risky decision-making, the neural mechanisms through which external information is integrated in that process had not been studied before this," says Berns.

A new approach to prostate cancer detection

On Friday 20 March, US researcher Dr. Chris Beecher from the University of Michigan gave a well attended lecture about sarcosine, an N-methyl derivative of the amino acid glycine, at the 24th Annual EAU Congress in Stockholm, Sweden. Dr Beecher is a colleague of lead author Dr. Arun Sreekumar. The research of Sreekumar, Beecher and their team looked at more than 1,000 small molecules in tissues associated with prostate cancer. These findings suggest that not only is sarcosine a marker of cancer aggressiveness, it also has a role in endowing a cancer with malignant properties. Sreekumar´s publication in Nature (457, 12 February 2009: 910-914) has attracted a lot of scientific and also popular attention. The EAU Scientific Congress Office inserted a special breaking news session in the congress programme in order to present the most updated scientific information in Stockholm. Sarcosine may distinguish slow-growing prostate cancers from those likely to spread and become lethal. Conveniently, sarcosine can be identified in urine, a less invasive test than the blood analysis needed for the standard prostate-specific antigen (PSA), a protein produced by the cells of the prostate gland. PSA is present in small quantities in the serum of healthy men, and is often elevated in the presence of prostate cancer. Quite often men have PSA scores that fall into a grey area. Therefore, invasive biopsy is needed to clarify a diagnosis.

HIV-1 protease inhibitor induced oxidative stress in pancreatic B-cells

Researchers at the Tulane University School of Medicine, New Orleans, Louisiana have discovered that the HIV-1 protease inhibitors (PIs), such as nelfinavir included in highly active antiretroviral therapy (HAART) regimen for the treatment of HIV-1 patients, induce deleterious effects on insulin secretion mediated through the oxidative stress pathway. They report a significant decrease in the levels of the antioxidants, cytosolic superoxide dismutase (Cu/Zn SOD) and glutathione, whereas mitochondrial SOD levels remained unaffected in pancreatic beta-cells (INS-1 cells) exposed to nelfinavir. However, the mitochondrial uncoupling protein (UCP2) levels were up-regulated during nelfinavir induced oxidative stress and directly affected the ATP levels in these cells. A significant decrease in ATP production was also observed which may account for the decrease in glucose stimulated insulin secretion upon nelfinavir treatment. This study appears in the April 2009 issue of Experimental Biology and Medicine. Although insulin resistance has been clinically observed in HIV-1 patients receiving HAART regimen, the molecular mechanisms of this metabolic abnormality have not been delineated.

New drug agent knocks out multiple enzymes in cancer pathway

A team of 24 researchers from the U.S., Europe, Taiwan and Japan and led by University of Illinois scientists has engineered a new anti-cancer agent that is about 200 times more active in killing tumor cells than similar drugs used in recent clinical trials.The study appears this week in the Journal of the American Chemical Society. The new agent belongs to a class of drugs called bisphosphonates. These compounds were originally developed to treat osteoporosis and other bone diseases, but were recently found to also have potent anti-cancer and immune boosting properties. Drug developers have tried for years to design drugs to inhibit cell survival pathways in tumor cells, focusing on a protein called Ras since nearly a third of all human cancers involve a mutation in the Ras gene that causes cell signaling to go awry. These efforts have met with limited success. Bisphosphonates act on other enzymes, called FPPS and GGPPS, which are upstream of Ras in the cell survival pathway. Inhibiting these enzymes appears to be a more effective strategy for killing cancer cells. When used in combination with hormone therapy in a recent clinical trial, the bisphosphonate drug zoledronate significantly reduced the recurrence of breast cancer in premenopausal women with estrogen-receptor-positive breast cancer. Similar results were reported previously for hormone-refractory prostate cancer. But zoledronate quickly binds to bone, reducing its efficacy in other tissues.

Energy drinks may be harmful to people with hypertension, heart disease

People who have high blood pressure or heart disease should avoid consuming energy drinks, according to a Henry Ford Hospital study to be published online Wednesday in the Annals of Pharmacotherapy.
Researchers found that healthy adults who drank two cans a day of a popular energy drink experienced an increase in their blood pressure and heart rate. No significant changes in EKG measurements were reported.
The increases in blood pressure and heart rate were insignificant for healthy adults, but could prove harmful to people with a heart-related condition, says James Kalus, Pharm.D., senior manager of Patient Care Services at Henry Ford Hospital and lead author of the study. "Based on our findings, we recommend that people who have hypertension or heart disease and are taking medication for them to avoid consuming energy drinks because of a potential risk to their health," Dr. Kalus says. Researchers believe the caffeine and taurine levels in energy drinks could be responsible for increases in blood pressure and heart rate. The brand of energy drink used in the study is not being identified because most energy drinks on the market boast similar levels of caffeine and taurine, a non-essential amino acid derivative often found in meat and fish. The caffeine levels in energy drinks are equivalent to at least one to two cups of coffee. Dr. Kalus says energy drinks should not be confused with sports drinks, which aim to replenish the carbohydrates and electrolytes that a body needs.

UC San Diego Biologists Discover a Protein Link to Wound Healing

Diabetes and eczema may appear to be two completely unrelated diseases. But UC San Diego biologists have uncovered what appears to be a crucial biochemical link between the two.The scientists report in the March 26 issue of the journal Nature their discovery that a protein previously linked only to cell death, plays a critical role in the healing of wounds in laboratory mice. This protein, known as caspase 8, is deficient in humans with eczema, but produced in excess amounts by diabetics. The researchers say their discovery may explain why many diabetics lack a normal wound response and suffer severe complications from minor cuts and scrapes, and why those with eczema exhibit a chronic inflammation of the skin that compromises its protective function.

'Master regulator' of skin formation discovered

Researchers at Oregon State University have found one gene in the human body that appears to be a master regulator for skin development, in research that could help address everything from skin diseases such as eczema or psoriasis to the wrinkling of skin as people age. Inadequate or loss of expression of this gene, called CTIP2, may play a role in some skin disorders, scientists believe, and understanding the mechanisms of gene action could provide a solution to them. "We found that CTIP2 is a transcriptional factor that helps control different levels of skin development, including the final phase of a protective barrier formation," said Arup Indra, an OSU assistant professor of pharmacy. "It also seems particularly important in lipid biosynthesis, which is relevant not only to certain skin diseases but also wrinkling and premature skin aging."
The findings of this research, done in collaboration with Mark Leid, OSU professor of pharmacy, were recently published in the Journal of Investigative Dermatology. This work is supported by the National Institutes of Health, which has provided $1.5 million for its continuation. Skin is actually the largest organ in the human body, and has important functions in protecting people from infection, toxins, microbes and solar radiation. But it's not static – skin cells are constantly dying and being replaced by new cells, to the extent that human skin actually renews its surface layers every three to four weeks. Wrinkles, in fact, are a reflection of slower skin regeneration that occurs naturally with aging. Major advances have been made in recent years in understanding how skin develops in space and time, and in recent breakthroughs scientists learned how to re-program adult skin cells into embryonic stem cells.

Inconsistent performance speed among children with ADHD may underlie how well they use memory

Children with attention-deficit hyperactivity disorder (ADHD) show more variable or inconsistent responses during on ‘working’ or short-term memory tasks when compared with typically developing peers, a study by UC Davis M.I.N.D. Institute Julie Schweitzer has found. “We think poor working memory is a characteristic present in many children and adults with ADHD,” said Schweitzer, an associate professor in the Department of Psychiatry and Behavioral Sciences. “Our study helps explain why working memory may be fine at one moment and poor at another, just as one day a child with ADHD seems to be able to learn and focus in class and on another day seems distracted and not paying attention,” Schweitzer said. According to the national Centers for Disease Control and Prevention (CDC), an estimated 4.4 million youth, ages 4 to17, have been diagnosed with ADHD by a healthcare professional. In 2003 nearly 8 percent of school-aged children were reported to have an ADHD diagnosis by their parent. The current study, published online in February in the journal Child Neuropsychology, supports the idea that what underlies impaired working memory is a problem in how consistently a child with ADHD can respond during a working memory task. “We have known for some time that children with ADHD vary in how fast they are able to complete working memory tasks when compared to normally developing control subjects,” Schweitzer explained .

Tell me where you research and I’ll tell you who you work with

A joint project by the Carlos III University, the University of Extremadura and the Spanish National Research Council (CSIC) has analysed researchers’ preferences when it comes to seeking partners to co-author articles. Catalonia and Cantabria are the two regions with the most active researchers, while those in the Balearic Islands rely most on international colleagues.Scientists at Madrid’s Carlos III University, the University of Extremadura and the CSIC’s Institute of Public Goods and Policies have collaborated to produce a study called An Examination of scientific university co-authorship in Spain, which has analysed patterns of inter-university collaboration in the country. The social networks model was used to carry out the study. The research project, published in the latest issue of the journal Aslib Proceedings, analyses all the issues relating to the production of scientific work in Spain – the number of projects conducted without collaboration, the places where participating researchers tend to come from, and the factors governing the origin of the researchers chosen. The study’s authors, Carlos Olmeda, Antonio Perianes and Mª Antonia Ovalle, tell SINC that “we were interested in looking into unknowns such as the degree of cooperation in co-authorship practices between Spanish university researchers at national level, to see whether there is a hierarchy in terms of collaboration between Spanish universities, and to analyse the impact of collaborative production”.The study’s conclusions show that, in Spain, “six out of every ten articles are written in collaboration, and three out of every ten with international partners”.

The egg makes sure that sperm don't get too old

In contrast to women, men are fertile throughout life, but research at the Sahlgrenska Academy, University of Gothenburg, Sweden, has now shown that a fertilising sperm can get help from the egg to rejuvenate. The result is an important step towards future stem cell therapy. The risk of chromosomal abnormalities in the foetus is highly correlated to the age of the mother, but is nearly independent of the age of the father. One possible explanation is that egg cells have a unique ability to reset the age of a sperm. "We are the first to show that egg cells have the ability to rejuvenate other cells, and this is an important result for future stem cell research", says Associate Professor Tomas Simonsson, who leads the research group at the Sahlgrenska Academy that has made this discovery. Each time a cell divides, the genetic material at the ends of the chromosomes becomes shorter. The ends of the chromosomes, known as "telomeres", are important for the genetic stability of the cell and they act as a DNA clock that measures the age of the cell. The cell stops dividing and dies when the telomeres become too short. The discovery that the egg cell can extend the telomeres of a fertilising sperm cell is important in the development of stem cell therapy. Stem cell therapy involves replacing the cell nucleus in unfertilised egg with a nucleus from a somatic cell that has come from a patient who needs a stem cell transplantation. As soon as the cell has divided a few times, it is possible to harvest stem cells that are then allowed to mature to the cell type that the recipient needs.

Westminster showcase for animal replacement research

Researchers from The University of Nottingham will be in Westminster today to talk to MPs about how innovative scientific advances could reduce the need for animal experimentation in the quest to find new treatments for the painful degenerative joint condition osteoarthritis. Dr Ali Mobasheri, Associate Professor and Reader in Comparative Physiology at the University’s School of Veterinary Medicine and Science, and PhD postgraduate student Abigail Clutterbuck will showcase their research at a poster event organised by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) in the House of Lords. Their work has been chosen as fine examples of research supporting the ethos of the centre, which provides a UK focus for the promotion, development and implementation of the 3Rs — replacement, refinement and reduction — in animal research and testing. Dr Mobasheri and Abigail both conduct research into developing our understanding of osteoarthritis, a painful and debilitating condition, which is the most common cause of joint disease in both humans and pets. It is hoped that by finding out more about how the condition progresses, new treatments and therapies can be developed to help relieve the symptoms of sufferers, which can include pain, inflammation and loss of mobility.

Daily consumption of cannabis predisposes to the appearance of psychosis and schizophrenia

The daily consumption of cannabis predisposes to the appearance of psychosis and schizophrenia, and those episodes of psychosis which are fruit of this substance present certain specific characteristics, both before their appearance and in the clinical presentation of the psychosis. This is one of the conclusions of the doctoral thesis "Neurodevelopment and environmental stress in initial psychosis: transversal analysis of the ESPIGAS study", carried out by researcher Miguel Ruiz Veguilla, of the Institute of Neurosciences of the University of Granada (Spain) and supervised by professors Manuel Gurpegui Fernández de Legaria and Jorge Cervilla Ballesteros. Ruiz Veguilla is also the person in charge fo the Unit of Development Neuropsychiatry of Jaén (Spain). This work has studied the risk factors associated with schizophrenia, identifying and characterizing in depth those psychosis associated with a continual consumption of cannabis. They carried out a study with 92 subjects, 50 of which had developed a psychosis without presenting signs of an "abnormal neurodevelopment", this is, they had been doing well academically, they had a group of friends (no social isolation) and they presented a good motor coordination. In addition, these subjects did not show a family history of episodes of psychosis in first or second degree.

Fructose metabolism by the brain increases food intake and obesity

The journal Biochemical and Biophysical Research Communications (http://www.elsevier.com/locate/ybbrc) (BBRC), published by Elsevier, will publish an important review this week online, by M. Daniel Lane and colleagues at Johns Hopkins, building on the suggested link between the consumption of fructose and increased food intake, which may contribute to a high incidence of obesity and Type 2 diabetes. Over the past four decades life-styles have gravitated toward the excessive consumption of 'high energy' foods and sedentary behavior that has resulted in a high incidence of obesity and its pathological consequences. This scenario has led to the increased occurrence of insulin resistance and Type 2 diabetes. At present, approximately thirty percent of adult Americans can be classified as obese. Moreover, these changes now extend into the younger age group.M. Daniel Lane and co-workers at The Johns Hopkins University School of Medicine in Baltimore have now pulled together work, largely in their laboratory (many papers beginning in 2000), dealing with the role of malonyl-CoA in the signaling system in the brain (specifically the hypothalamus) that has inputs into the higher brain centers that determine feeding behavior, most notably appetite. Two papers in the journal PNAS in 2007 and 2008 showed that glucose and fructose act quite differently in the brain (hypothalamus) - glucose decreasing food intake and fructose increasing food intake. Both of these sugars signal in the brain through the malonyl-CoA signaling pathway and have inverse effects on food intake.Lane commented "We feel that these findings may have particular relevance to the massive increase in the use of high fructose sweeteners (both high fructose corn syrup and table sugar) in virtually all sweetened foods, most notably soft drinks. The per capita consumption of these sweeteners in the USA is about 145 lbs/year and is probably much higher in teenagers/youth that have a high level of consumption of soft drinks. There is a large literature now that correlates, but does not prove that a culprit in the rise of teenage obesity may be fructose."The fact that fructose metabolism by the brain increases food intake and obesity risk raises health concerns in view of the large and increasing per capita consumption of high fructose sweeteners, especially by youth.

Queen's scientists find new way to battle MRSA

Experts from Queen's University Belfast have developed new agents to fight MRSA and other hospital-acquired infections that are resistant to antibiotics. The fluids are a class of ionic liquids that not only kill colonies of these dangerous microbes, they also prevent their growth. The development of these new antimicrobial agents was carried out by a team of eight researchers from the Queen's University Ionic Liquid Laboratories (QUILL) Research Centre. The team was led by Brendan Gilmore, Lecturer in Pharmaceutics at the School of Pharmacy, and Martyn Earle, Assistant Director of QUILL. The discovery is published in the scientific journal Green Chemistry. Many types of bacteria, such as MRSA, exist in colonies that adhere to the surfaces of materials. The colonies often form coatings, known as biofilms, which protect them from antiseptics, disinfectants, and antibiotics. Earle said "We have shown that when pitted against the ionic liquids we developed and tested, biofilms offer little or no protection to MRSA, or to seven other infectious microorganisms."
Ionic liquids, just like the table salt sprinkled on food, are salts. They consist entirely of ions - electrically-charged atoms or groups of atoms. Unlike table salt, however, which has to be heated to over 800o C to become a liquid, the ionic liquid antibiofilm agents remain liquid at the ambient temperatures found in hospitals. One of the attractions of ionic liquids is the opportunity to tailor their physical, chemical, and biological properties by building specific features into the chemical structures of the positively-charged ions (the cations), and/or the negatively-charged ions (the anions).Earle said "Our goal is to design ionic liquids with the lowest possible toxicity to humans while wiping out colonies of bacteria that cause hospital acquired infections."

Stopping autoimmunity before it strikes

Current research describes a new method to track the development of autoimmune diseases before the onset of symptoms. The related report by Zangani et al, "Tracking early autoimmune disease by bioluminescent imaging of NF-?B activation reveals pathology in multiple organ systems," appears in the April 2009 issue of The American Journal of Pathology. Autoimmune diseases such as lupus, multiple sclerosis, rheumatoid arthritis and diabetes are caused when the immune system attacks the body's own cells. Normally, immune cells are prevented from attacking normal cells; however, in patients with autoimmune disease, this "tolerance" is lost. The immediate causes of autoimmune diseases remain unknown, partially due to the inability to detect disease before the onset of symptoms. Early detection of autoimmune disease is critical for assessing new treatments. The molecule NF-?B is activated by inflammation, which plays a key role in autoimmune disease development, making NF-?B a prime candidate to track autoimmune activity. Researchers at the University of Oslo led by Drs. Ludvig Munthe and Bjarne Bogen in collaboration with Rune Blomhoff engineered NF-?B such that it would emit light when activated. Using a mouse model of systemic autoimmunity with features of lupus, they found that NF-?B activation signals were present in affected organs several weeks before the clinical manifestations of disease. The light signal intensity correlated with disease progression. NF-?B tracking may therefore provide a new tool in the evaluation of early autoimmune therapies.

Discovery may result in new test to determine predisposition to cancer

Researchers at UCLA's Jonsson Comprehensive Cancer Center have developed an assay that may be used to help identify new genes that can predict a predisposition to cancer. The study, published in the April issue of Radiation Research, was done in yeast and mammalian cells. Cancer cells show persistent genetic instability and the researchers, led by Robert Schiestl, have discovered a mechanism that switches on that genetic instability. If they can uncover and understand the molecular pathways at work in promoting genetic instability, they may be able to develop ways to switch that mechanism off, restoring stability.
"We all have several hundred cells in our body that go crazy every day, and they're taken out by our immune system," said Schiestl, a professor of pathology, radiation oncology and environmental health sciences and a Jonsson Cancer Center scientist. "What's important is that those cells don't grow and spread and invade other regions of our body. Cancer cells are able to grow, spread and invade because the continued genetic instability can disturb the cellular program and create a growth advantage. Unfortunately, the immune system is not very effective at taking cancer cells out." The assay determines the efficiency of the repair mechanism when DNA suffers a double-strand break, when both strands in the double helix are severed. These breaks cause genetic instability and are particularly dangerous because they can lead to genome rearrangements or deletions of certain genes that, when gone, result in cancer. "Every cell has double strand breaks all the time," said Schiestl, senior author of the study. "It is how the cell tries to fix these breaks that is key, the capacity and the efficiency of the repair so no further harm occurs."

Imaging technique may trace development of Parkinson's disease

While finding a biomarker for Parkinson's disease that would let physicians screen for or track its progression remains an elusive goal, a team led by a University of Illinois at Chicago neuroscientist has shown that a non-invasive brain scanning technique offers promise. The tool may also help advance the development of new drugs or neuroprotective agents to treat or ward off Parkinson's. The findings, now online, will appear in a forthcoming issue of Neurology. David Vaillancourt, assistant professor of kinesiology at UIC, along with colleagues from UIC and Rush University, used a type of MRI scan called diffusion tensor imaging on 28 subjects, half with early symptoms of Parkinson's and the other half without. They scanned an area of the brain called the substantia nigra, a cluster of neurons that produce the neurotransmitter dopamine. Parkinson's patients have been found to have about half the number of dopaminergic neurons in certain areas of the substantia nigra as those without the disease. Determining loss of dopaminergic neurons using conventional methods such as metabolic PET scans is expensive, invasive, and requires injection of radioactive tracer chemicals. But the method studied by Vaillancourt and his group is non-invasive, relatively inexpensive, and does not use radioactive tracers. "We're suggesting it's possible to eventually diagnose Parkinson's disease non-invasively and objectively by examining the part of the brain thought to underlie the causes of the disease," said Vaillancourt. No tool currently available can do that, he said.

Hopkins scientists ID 10 genes associated with a risk factor for sudden cardiac death

One minute, he's a strapping 40-year-old with an enviable cholesterol level, working out on his treadmill. The next, he's dead. That an abnormality in his heart's electrical system had managed to stay on the Q.T. — until it proved lethal — is characteristic of sudden cardiac death, which annually claims more than a quarter million Americans. A dearth of discernable symptoms and lack of detectable molecules circulating in the blood makes the prediction of sudden cardiac death largely dependent on genetic risk factors. Having identified 10 common variants of genes that modify the timing of the contraction of the heart, known as the QT interval, scientists in the Johns Hopkins University School of Medicine, in collaboration with an international contingent of researchers, now provide new insight about the underpinnings of the QT interval which, when prolonged or shortened, predisposes to sudden cardiac death. QT interval, which is determined from a standard electrocardiogram (ECG), reflects the time it takes for the heart (ventricles) to contract and then reset for the next heartbeat. Publishing March 22 in Nature Genetics, the international team including researchers from the Technical University in Munich, Johns Hopkins and others, used DNA samples previously collected for epidemiological studies to analyze the genomes of 15,842 individuals whose QT intervals had been measured by electrocardiogram. With DNA microarray chips, each able to assess hundreds of thousands of markers in each sample, followed by bioinformatic techniques to increase the number of markers, the researchers screened approximately 2.5 million markers to detect subtle alterations in the sequences of these genomes that modify the QT interval. By focusing on 2.5 million sites in a genome of 3 billion sites, the scientists surveyed one-one-thousandth of nearly 16,000 genomes. This relatively small but "still extremely powerful" screen correlates genomic architecture with QT intervals, according to Aravinda Chakravarti, Ph.D., a professor in the McKusick-Nathans Institute of Genetic Medicine.

New method of assessing women's eggs could enhance IVF success

Many couples who have trouble conceiving a child have turned to a process known as in vitro fertilization. The resulting embryos are then transferred back into the woman or placed in storage. More than 400,000 embryos are currently in storage in the United States. The quality of the egg is often the single greatest factor in the viability of the embryo, yet fertility experts lack a good method for assessing the eggs.
Barry Behr, PhD, HCLD, associate professor of obstetrics and gynecology at the Stanford University School of Medicine and director of Stanford's IVF laboratory, recently published findings on a way to "profile" the eggs to determine which are more likely to result in pregnancies.The question - Can a non-invasive test of a woman's eggs be used to predict in vitro fertilization success? Background - In vitro fertilization involves retrieving eggs from a woman's ovaries and fertilizing the eggs in a dish by incubating them with sperm or injecting sperm directly into them. The resulting embryos are then transferred back into the woman or placed in storage. The quality of the egg is often the single biggest determinant in the viability of the embryo.The need - There is currently no good tool to available to assess eggs. "We would stand on our head and hop on our left leg if we could find a way to give us some information about viability of embryo," said Behr. The technology - Metabolomic testing reveals trace molecules remaining after an array of cellular processes. Previous studies have shown that metabolomic profiling can be used to identify unique biomarkers left behind by embryos in culture, which foretell the embryos with the highest reproductive potential in IVF. "Think of it as a sort of smog test for the embryo," said Behr. "It tells you how clean the engine is burning, and whether there are any problems."The study - The study involved extracting eggs from 43 women, incubating them in culture for three hours and then examining their metabolomic results before fertilization. The researchers then documented what happened to each egg: Whether it was fertilized, the quality of the resulting embryo on days three and five, and whether it led to a successful pregnancy.

Stanford study improves insights into Parkinson's disease and possible treatments

About the only thing doctors have understood about deep-brain stimulation, which is widely used to treat Parkinson’s disease symptoms, is that somehow it works for many patients. In a new study that was published March 19 in the online journal Science Express, Stanford University researchers used light to illuminate how the treatment works, generating surprising insights into the diseased circuitry and also suggesting new ideas to improve Parkinson’s therapy.Parkinson’s disease is a brain disorder that affects an estimated 1.5 million Americans, causing tremors, stiffness and difficulty balancing. In those who undergo deep-brain stimulation, pulses of electricity are applied to the circuitry of a tiny brain region called the subthalamic nucleus. Naturally, researchers suspected that cells within that region are somehow stimulated, or calmed, by the shocks, leading to reduced Parkinson’s symptoms. In the new study, which will also appear in an upcoming print issue of Science, the medical and engineering researchers found that by far the biggest effect in “Parkinsonian” rodents occurs not by stimulating cells in the subthalamic nucleus, but by stimulating the neural wires, called axons, that connect directly to it from areas closer to the surface of the brain.

Strategy Discovered for Fighting Persistent Bacterial Infections

Researchers at National Jewish Health have discovered a promising strategy for destroying the molecular scaffolding that can make Pseudomonas bacterial infections extremely difficult to treat in cystic fibrosis patients, wearers of contact lenses, and burn victims. Jerry Nick, MD, Associate Professor of Medicine at National Jewish Health, and his colleagues report in the April 2009 issue of The Journal of Medical Microbiology that a long string of aspartic acid molecules disrupts the molecular bonds that hold together the structure supporting Pseudomonas biofilms. "Once a bacterial community forms a biofilm it becomes much more difficult to treat," said Dr. Nick. "We think our discovery will pave the way for more effective treatment of Pseudomonas aeruginosa infections, which can wreak so much havoc in cystic fibrosis patients."
Biofilms are a form of bacterial colony in which bacterial cells attach to and live within an extracellular matrix, where medications and the immune system have difficulty reaching them. As a result, these infections become very difficult to treat effectively. Pseudomonas biofilms form and cause lung damage in most cystic fibrosis patients as they grow older. Pseudomonas biofilms can also form on the corneas of contact lens wearers, and in wounds and burns. Dr. Nick and his colleagues previously showed that formation of Pseudomonas aeruginosa biofilms is enhanced by the remains of immune system cells known as neutrophils, which accumulate in vast numbers to the site of infection, then die and spill their contents. Pseudomonas builds the extracellular matrix from neutrophils' DNA, the actin structural molecules, and histones, the molecules around which DNA normally wraps inside the cell nucleus.

New Stem Cell Therapy May Lead To Treatment for Deafness

Deafness affects more than 250 million people worldwide. It typically involves the loss of sensory receptors, called hair cells, for their “tufts” of hair-like protrusions, and their associated neurons. The transplantation of stem cells that are capable of producing functional cell types might be a promising treatment for hearing impairment, but no human candidate cell type has been available to develop this technology. A new study led by Dr. Marcelo N. Rivolta of the University of Sheffield has successfully isolated human auditory stem cells from fetal cochleae (the auditory portion of the inner ear) and found they had the capacity to differentiate into sensory hair cells and neurons. The study is published in the April issue of STEM CELLS. The researchers painstakingly dissected and cultured cochlear cells from 9-11 week-old human fetuses. The cells were expanded and maintained in vitro for up to one year, with continued division for the first 7 to 8 months and up to 30 population doublings, which is similar to other non-embryonic stem cell populations, such as bone marrow. Gene expression analysis showed that all cell lines expressed otic markers that lead to the development of the inner ear as well as markers expressed by pluripotent embryonic stem cells, from which all tissues and organs develop. They were able to formulate conditions that allowed for the progressive differentiation into neurons and hair cells with the same functional electrophysiological characteristics as cells seen in vivo.

Inhaling A Heart Attack - How Air Pollution Can Cause Heart Disease

We are used to thinking of heart disease as a product of genetic factors or lifestyle choices, such as what we eat and how much we exercise. There is another road to heart disease: breathing. Accumulating evidence indicates that an increase in particulate air pollution is associated with an increase in heart attacks and deaths. Research has begun in the relatively new field of environmental cardiology -- a field that examines the relationship between air pollution and heart disease. Aruni Bhatnagar of the University of Louisville and Robert Brook of the University of Michigan have organized a symposium Environmental Factors in Heart Disease, to take place April 21 at the Experimental Biology conference in New Orleans. The American Physiological Society is one of the sponsors of the annual conference. Dr. Bhatnagar will speak on Environmental aldehydes exposure and cardiovascular disease, while Dr. Brook will give a talk on Environmental pollution and hypertension. In addition, Araujo Jesus of UCLA will speak on Exacerbation of experimental atherogenesis by ultrafine air pollution, and Murray Mittleman of the Harvard School of Public Health will speak on Air pollution and stroke.

Alcohol 'flush' signals increased cancer risk among East Asians

Many people of East Asian descent possess an enzyme deficiency that causes their skin to redden, or flush, when they drink alcohol. Scientists from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and Japan's Kurihama Alcohol Center now caution that heavy alcohol consumption greatly increases the risk for esophageal cancer among such individuals, who comprise about 8 percent of the world's population. Their review of recent research on this topic appears in the March 24, 2009 issue of PLoS Medicine. NIAAA is part of the National Institutes of Health. "It is very important for clinicians who treat patients of East Asian descent to be aware of the risk of esophageal cancer from alcohol consumption in their patients who exhibit the alcohol flushing response, so they can counsel them about limiting their drinking," says NIAAA Acting Director Kenneth R. Warren, Ph.D. First author Philip J. Brooks, Ph.D., of NIAAA's Laboratory of Neurogenetics, and his colleagues note that a clinician can reliably determine whether a patient is at risk simply by asking about previous episodes of facial flushing after drinking alcohol. Considered from this perspective, the authors point out, the flushing response is a clinically useful biomarker of genetic susceptibility to esophageal cancer risk from alcohol.Dr. Brooks cites the high mortality from esophageal cancer and the large number of individuals with the deficient enzyme, known as aldehyde dehydrogenase 2 (ALDH2). "Cancer of the esophagus is particularly deadly, with five-year survival rates ranging from 12 to 31 percent throughout the world. And we estimate that at least 540 million people have this alcohol-related increased risk for esophageal cancer," he notes. "We hope that, by raising awareness of this important public health problem, affected individuals who drink will reduce their cancer risk by limiting their alcohol consumption." Dr. Brooks and his colleagues explain that ALDH2 plays an important role in alcohol metabolism. When alcohol is consumed, it is first metabolized into acetaldehyde, a chemical similar to formaldehyde, which causes DNA damage and has other cancer-promoting effects. ALDH2 is the main enzyme responsible for breaking down acetaldehyde into acetate, a non-toxic metabolite in the body. East Asians have two main variants of the ALDH2 gene -- one that produces an enzyme with normal activity, and another that results in an inactive enzyme. When individuals with the inactive variant drink alcohol, acetaldehyde accumulates in the body, resulting in facial flushing, nausea, and rapid heartbeat. For people with two copies of the inactive variant, these symptoms are so severe that they can drink very little alcohol. However, individuals with only one copy of the inactive variant can become tolerant to the unpleasant effects of acetaldehyde, which puts them at risk for alcohol-related esophageal cancer.

Brain wave patterns can predict blunders, new study finds

A distinct alpha-wave pattern occurs in two brain regions just before subjects make mistakes on attention-demanding tests, according to a new study by researchers from the University of California, Davis, and the Donders Institute.From spilling a cup of coffee to failing to notice a stop sign, everyone makes an occasional error due to lack of attention. Now a team led by a researcher at the University of California, Davis, in collaboration with the Donders Institute in the Netherlands, has found a distinct electric signature in the brain which predicts that such an error is about to be made. The discovery could prove useful in a variety of applications, from developing monitoring devices that alert air traffic control operators that their attention is flagging, to devising new strategies to help children cope with attention deficit hyperactivity disorder (ADHD). The work will be posted online on March 23 by the journal Human Brain Mapping as part of a special issue highlighting innovations in electromagnetic brain imaging that will be published in May. How the brain responds to mistakes has been the subject of numerous studies, said Ali Mazaheri, a research fellow at the UC Davis Center for Mind and Brain. "But what I was looking for was the state the brain is in before a mistake is made," he said, "because that's what can tell us what produces the error." Working with colleagues at the Donders Institute for Brain, Cognition and Behavior at Radboud University, where he was a Ph.D student at the time, Mazaheri recruited 14 students into his study. While they took an attention-demanding test, Mazaheri recorded their brain activity using MEG — magnetoencephalography — a non-invasive brain-wave recording technique similar to, but more sensitive than electroencephalography (EEG), the technique commonly used in hospitals to detect seizures.

Molecular fingerprints point the way to earlier cancer diagnosis and more targeted treatment

Metabolites are molecular fingerprints of what your cells are up to and Dr. Arun Sreekumar wants to know the impression made by cancer. You've likely heard about metabolites; your physician probably screens for some known ones such as triglycerides or cholesterol at your annual physical. Scientists suspect we have about 3,000 metabolites that come from our food or are synthesized from different compounds in our bodies.
Dr. Sreekumar, a cancer researcher at the Medical College of Georgia Cancer Center, wants those screens of the blood or urine to also detect early signs of cancers such as leukemia, bladder, kidney and breast when the chance for cure is best. He's already begun to identify metabolites that indicate not only the presence of prostate cancer, but its aggressiveness, a tool that could help tailor optimal treatment. The search began in men at risk: those with elevated prostate specific antigen, or PSA, levels. A PSA test along with a digital rectal exam is today's standard for prostate screening so physicians typically do both in men age 50 and older. But PSA levels are actually better at helping determine if prostate cancer has returned, Dr. Sreekumar says. Elevated levels of PSA, a protein, are not always predictive of cancer, which means a lot of men get unnecessary biopsies. PSA measurements also can't distinguish between tumors that have a good outcome versus those with a poor one.

Stroke survivors improve balance with tai chi

Stroke can impair balance, heightening the risk of a debilitating fall. But a University of Illinois at Chicago researcher has found that stroke survivors can improve their balance by practicing the Chinese martial art of tai chi. Christina Hui-Chan, professor and head of physical therapy at UIC, has studied and used tai chi as a way to improve balance and minimize falls among healthy elderly subjects. Now she and a colleague have seen similar results in a group of stroke survivors. The study used 136 subjects in Hong Kong who had suffered a stroke more than six months earlier. Participants were randomly assigned to a tai chi group or a control group that practiced breathing, stretching and other exercises that involved sitting, walking, memorizing and reasoning.Tai chi consists of constant coordinated movement of the head, trunk and limbs requiring tremendous concentration and balance control. Participants learned a simplified form that had been shown to be beneficial to arthritis patients. Patients were trained in small groups by physical therapists in a weekly class, then practiced at home three days a week for one hour. They received 12 weeks of training but were able to learn the technique in as little as eight. The goal was to make the patients as independent in their treatment as possible, Hui-Chan said. They were then tested for their ability to maintain balance while shifting weight, leaning in different directions, and standing on moving surfaces to simulate a crowded bus. In these tests the tai chi group out-performed the control exercise group. The two groups performed about the same on another test, which was not focused solely on balance but involved sitting, standing, walking, and returning to sit down. "The tai chi group did particularly better in conditions that required them to use their balance control," Hui-Chan said. "In only six weeks, we saw significant improvements. The ability to shift your weight is very important because all reaching tasks require it."

New research highlights dramatically reduced risk of developing dementia

People with memory problems are less at risk of developing dementia than previously thought, a new study led by the University of Leicester and Nottinghamshire Healthcare NHS Trust reveals.The five year research published in Acta Psychiatrica Scandinavica analysed data from 41 studies and dovetails with a Government focus to establish memory clinics in every town in the UK. The research led by Dr Alex Mitchell from the University of Leicester Department of Cancer Studies and Molecular Medicine was carried out with Dr. Shiri-Feshki of Nottinghamshire Healthcare NHS Trust. Dr Mitchell said "This new research suggests that people with mild cognitive impairment (MCI) appear to have a lower risk of progressing to dementia than previously believed. "Mild cognitive impairment (MCI) is an important disorder of memory and related areas found in about 1 in 6 people seen in general practice. The condition can occur in mid or late life and until recently most doctors told people with MCI that their risk of developing dementia was up to 15% per year making deterioration almost inevitable within 5 to 10 years. "Our research found that the proportion of people who progressed was 10% per year in high risk groups and in fact only 5% per year in low risk groups. Moreover only a minority (20-40%) of people developed dementia even after extended follow-up and the risk appeared to reduce slightly with time. "These results should be seen as positive for those with memory problems even for those that struggle with the kind of memory tests given by the GP or in a memory clinic. There is a large effort to find out who is most at risk of further decline as well to find strategies that might slow down such progress." GPs have often been reluctant to give a diagnosis of MCI because of its consequences but this current finding should encourage clinicians to identify people with memory problems. Many such individuals stay stable for a long period and a substantial number also improve.

Time (and PPAR-beta/delta) heals all wounds

Mammalian skin requires constant maintenance, but how do skin cells know when to proliferate and at what rate? In the March 23, 2009 issue of the Journal of Cell Biology, Nguan Soon Tan and colleagues reveal that skin fibroblasts use a protein called PPAR?/? to make sure overlying epithelial cells don't proliferate too quickly. Their results highlight how communications between different cell types are critical to maintain the skin as a barrier against the outside world. Skin has two main layers: the underlying dermis, made up of fibroblasts and other cells, and the outer epidermis, containing epithelial keratinocytes. Signals are exchanged between these layers to coordinate their function, but dissecting these signals is tricky. For example, PPAR?/? is an important protein for maintaining healthy skin, but its precise function remains controversial. PPAR?/? is a nuclear hormone receptor that regulates gene expression. In mice lacking PPAR?/?, epidermal cells proliferate excessively after wounding (1). But cultured keratinocytes from these mice don't proliferate any faster than normal cells and, in fact, are more susceptible to apoptosis (2). According to Nguan Soon Tan, this discrepancy was the first indication that PPAR?/? might regulate crosstalk between layers of the skin—the epidermal hyperproliferation seen in the knockout mice could be due to faulty signals from the dermal cells. But this couldn't be studied further in mice, as it is not yet possible to delete a gene exclusively from the dermis. "We had to look at a situation where the different types of cells were not in isolation but could communicate with each other," says Tan. "Organotypic skin cultures are a really good technique for this." First developed in the 1980s (3), organotypic skin cultures (OTCs) are made by embedding dermal fibroblasts in a gel of extracellular matrix proteins. Keratinocytes are seeded on top of this gel and the two cell types develop into an in vitro version of skin that looks remarkably like the real thing. The fibroblasts and keratinocytes can therefore be manipulated separately—knocking down or overexpressing proteins— before the skin is reconstructed.

New 'green' pesticides are first to exploit plant defenses in battle of the fungi

Exploiting a little-known punch/counterpunch strategy in the ongoing battle between disease-causing fungi and crop plants, scientists in Canada are reporting development of a new class of "green" fungicides that could provide a safer, more environmentally-friendly alternative to conventional fungicides. They will report on the first pesticides to capitalize on this unique defensive strategy here today at the 237th National Meeting of the American Chemical Society. Developed with sustainable agriculture in mind, the new fungicides — called "paldoxins" — could still do the work of conventional pesticides, helping to protect corn, wheat and other crops. These crops increasingly are used not just for food, but to make biofuels. The new fungicides also could help fight the growing problem of resistance, in which plant pests shrug off fungicides, the researchers suggest. Most fungicides today are made based on chemicals that can kill potentially beneficial organisms and have other adverse environmental effects. The new materials are more selective, stopping fungi that cause plant diseases without harming other organisms. They work in a unique way, disrupting a key chemical signalling pathway that the fungi use to breakdown a plant's normal defenses. As a result, the plants boost their natural defenses and overcome fungal attack without harming people and the environment, the researchers say. "Conventional fungicides kill constantly," explains study leader Soledade Pedras, Ph.D., a professor of chemistry at the University of Saskatchewan in Canada. "Our products only attack the fungus when it's misbehaving or attacking the plant. And for that reason, they're much safer." Researchers have known for years that many plants have a defense mechanism that involves production of natural chemicals, called phytoalexins, to kill disease-causing fungi. The fungus, however, fights back. It releases enzymes that detoxify, or destroy, the phytoalexin, leaving the plant vulnerable to the fungi's attack.

Scientists find cellular process that fights virus

Scientists have discovered a new way for our immune system to combat the elusive virus responsible for cold sores: Type 1 herpes simplex (HSV-1). As reported in the advance online edition of Nature Immunology, a group of virus hunters from the Université de Montréal, in collaboration with American colleagues, have identified a cellular process that seeks out and fights herpes. The five-year study, partially supported by the Canadian Institutes of Health Research, was a joint project with Washington University and Pennsylvania State University. "Once human cells are infected with Type 1 herpes simplex, the virus comes back because it hides and blocks protection from our immune system," says Luc English, the study's lead author and a doctoral student at the Université de Montréal's Department of Pathology and Cell Biology. "For the first time, our research team has indentified a combative cellular mechanism in this game of hide-and-seek." "We've found that the nuclear membrane of an infected cell can unmask Type 1 herpes simplex and stimulate the immune system to disintegrate the virus," says English. The team made its discovery while conducting various tests in HSV-1 infected mice cells. They replicated environments when Type 1 herpes simplex thrives, namely periods of low-grade fever between 38.5 to 39 degrees, and found that herpes-fighting mechanisms were unleashed. The research team now plans to study how activation of the herpes-combating cellular process could be applied to other illnesses. The outcome could hasten the development of therapies to prevent other immune-evading bacteria, parasites and viruses. "Our goal is to further study the molecules implicated in this mechanism to eventually develop therapies against diseases such as HIV or even cancer," says English.

Special gold nanoparticles show promise for 'cooking' cancer cells

Researchers are describing a long-awaited advance toward applying the marvels of nanotechnology in the battle against cancer. They have developed the first hollow gold nanospheres — smaller than the finest flecks of dust — that search out and "cook" cancer cells. The cancer-destroying nanospheres show particular promise as a minimally invasive future treatment for malignant melanoma, the most serious form of skin cancer, the researchers say. Melanoma now causes more than 8,000 deaths annually in the United States alone and is on the increase globally. The topic of a report presented here today at the American Chemical Society's 237th National Meeting, the hollow gold nanospheres are equipped with a special "peptide." That protein fragment draws the nanospheres directly to melanoma cells, while avoiding healthy skin cells. After collecting inside the cancer, the nanospheres heat up when exposed to near-infrared light, which penetrates deeply through the surface of the skin. In recent studies in mice, the hollow gold nanospheres did eight times more damage to skin tumors than the same nanospheres without the targeting peptides, the researchers say. "This technique is very promising and exciting," explains study co-author Jin Zhang, Ph.D., a professor of chemistry and biochemistry at the University of California in Santa Cruz. "It's basically like putting a cancer cell in hot water and boiling it to death. The more heat the metal nanospheres generate, the better." This form of cancer therapy is actually a variation of photothermal ablation, also known as photoablation therapy (PAT), a technique in which doctors use light to burn tumors. Since the technique can destroy healthy skin cells, doctors must carefully control the duration and intensity of treatment. Researchers now know that PATs can be greatly enhanced by applying a light absorbing material, such as metal nanoparticles, to the tumor. Although researchers have developed various types of metal nanoparticles to help improve this technique, many materials show poor penetration into cancer cells and limited heat carrying-capacities. These particles include solid gold nanoparticles and nanorods that lack the desired combination of spherical shape and strong near-infrared light absorption for effective PAT, scientists say.
To develop more effective cancer-burning materials, Zhang and colleagues focused on hollow gold nanospheres — each about 1/50,000th the width of a single human hair. Previous studies by others suggest that gold "nanoshells" have the potential for strong near-infrared light absorption. However, scientists have been largely unable to produce them successfully in the lab, Zhang notes. After years of research toward this goal, Zhang announced in 2006 that he had finally developed a nanoshell or hollow nanosphere with the "right stuff" for cancer therapy: Gold spheres with an optimal light absorption capacity in the near-infrared region, small size, and spherical shape, perfect for penetrating cancer cells and burning them up.

Proteins from garden pea may help fight high blood pressure, kidney disease

Researchers in Canada are reporting that proteins found in a common garden pea show promise as a natural food additive or new dietary supplement for fighting high blood pressure and chronic kidney disease (CKD). Those potentially life-threatening conditions affect millions of people worldwide. The study, which will be presented here today at the American Chemical Society's 237th National Meeting, is the first reporting that a natural food product can relieve symptoms of CKD, the scientists say. Peas long have been recognized as nutritional superstars, with healthful amounts of protein, dietary fiber, and vitamins wrapped in a low-fat, cholesterol-free package. The new research focuses on the yellow garden pea, a mainstay pea variety enjoyed as a veggie side-dish and used as an ingredient in dozens of recipes around the world. "In people with high blood pressure, our protein could potentially delay or prevent the onset of kidney damage," says study presenter Rotimi Aluko, Ph.D., a food chemist at the University of Manitoba in Winnipeg, Canada. "In people who already have kidney disease, our protein may help them maintain normal blood pressure levels so they can live longer." High blood pressure, or hypertension, is a major risk factor for CKD, a condition that has been affecting an increasing number of people in the United States and other countries. Estimates suggest that 13 percent of American adults — about 26 million people — have chronic kidney disease, up from 10 percent, or about 20 million people, in the 1990s. CKD is difficult to treat, and may progress to end-stage kidney disease that requires kidney dialysis or a kidney transplant. That situation is fostering a search for new ways of treating CKD and preserving kidney function. Working with University of Manitoba colleague Harold Aukema, Ph.D., Aluko purified a mixture of small proteins — called pea protein hydrolysate — from the yellow garden pea. The researchers fed small daily doses of the protein mixture to laboratory rats with polycystic kidney disease, a severe form of kidney disease used as a model for research on CKD. At the end of the 8-week-long study period, the protein-fed rats with kidney disease showed a 20 percent drop in blood pressure when compared to diseased rats on a normal diet, the researchers say. "This is significant because a majority of CKD patients actually die from cardiovascular complications that arise from the high blood pressure associated with kidney malfunction," Aluko notes. In both rats and humans with polycystic kidney disease, the condition causes urine output to be severely reduced and the kidneys are unable to properly remove dangerous toxins. The researchers showed that their pea extract caused a 30 percent boost in urine production in the diseased rats, bringing their urine to within normal levels. "That's a huge improvement," says Aluko, adding that there were no obvious adverse side effects from the pea protein.

Clinical trial backs use of special yogurt to fight stomach ulcer bacteria

Results of the first human clinical studies confirm that a new yogurt fights the bacteria that cause gastritis and stomach ulcers with what researchers describe as almost vaccine-like effects, scientists in Japan will report here today at the 237th National Meeting of the American Chemical Society. Researchers have long known that yogurt, a fermented milk product containing live bacteria, is a healthy source of calcium, protein, and other nutrients. Some brands of yogurt are now made with "probiotics" — certain types of bacteria — intended to improve health. The new yogurt represents a unique approach to fighting stomach ulcers, which affect 25 million people in the United States alone, and is part of a growing "functional food" market that now generates $60 billion in sales annually. "With this new yogurt, people can now enjoy the taste of yogurt while preventing or eliminating the bacteria that cause stomach ulcers," says study coordinator Hajime Hatta, Ph.D., a chemist at Kyoto Women's University in Kyoto, Japan. The new yogurt is already on store shelves in Japan, Korea, and Taiwan. The study opens the door to possible arrival of the product in the U.S., the researchers suggest. A type of bacteria called Helicobacter pylori (H. pylori) or over-use of aspirin and or other nonsteroidal antiinflammatory drugs, causes most stomach ulcers. H. pylori ulcers can be effectively treated and eliminated with antibiotics and acid suppressants. However, that simple regimen is unavailable to millions of poverty-stricken people in developing countries who are infected with H. pylori. New research also links childhood H. pylori infection to malnutrition, growth impairment and other health problems. As a result, scientists have been seeking more economical and convenient ways of dealing with these bacteria. In the new study, Hatta and colleagues point out that H. pylori seems to rely on a protein called urease to attach to and infect the stomach lining. In an effort thwart that protein, or antigen, Hatta turned to classic vaccine-making technology. They injected chickens with urease and allowed the chickens' immune systems to produce an antibody to the protein. The researchers then harvested the antibody, called IgY-urease, from chicken eggs. Hatta and colleagues theorized that yogurt containing the antibody may help prevent the bacteria from adhering to the stomach lining.

Gulf War veterans display abnormal brain response to specific chemicals

A new study by UT Southwestern Medical Center researchers is the first to pinpoint damage inside the brains of veterans suffering from Gulf War syndrome – a finding that links the illness to chemical exposures and may lead to diagnostic tests and treatments.Dr. Robert Haley, chief of epidemiology at UT Southwestern and lead author of the study, said the research uncovers and locates areas of the brain that function abnormally. Recent studies had shown evidence of chemical abnormalities and shrinkage of white matter in the brains of veterans exposed to certain toxic chemicals, such as sarin gas during the 1991 Persian Gulf War. The research, published in the March issue of the journal Psychiatry Research: Neuroimaging,enables investigators to visualize exact brain structures affected by these chemical exposures, Dr. Haley said.
"Before this study, we didn't know exactly what parts of the brain were damaged and causing the symptoms in these veterans," he said. "We designed an experiment to test areas of the brain that would have been damaged if the illness was caused by sarin or pesticides, and the results were positive." In designing the study, Dr. Haley and his colleagues reasoned that if low-level sarin or pesticides had damaged Gulf War veterans' brains, a likely target of the damage would be cholinergic receptors on cells in certain brain structures. If that was so, administering safe levels of medicines that stimulate cholinergic receptors would elicit an abnormal response in ill veterans. In the study, 21 chronically ill Gulf War veterans and 17 well veterans were given small doses of physostigmine, a substance which briefly stimulates cholinergic receptors. Researchers then measured the study participants' brain cell response with brain scans. "What we found was that some of the brain areas we previously suspected responded abnormally to the cholinergic challenge," Dr. Haley said. "Those areas were in the basal ganglia, hippocampus, thalamus and amygdala, and the thalamus. Changes in functioning of these brain structures can certainly cause problems with concentration and memory, body pain, fatigue, abnormal emotional responses and personality changes that we commonly see in ill Gulf War veterans." A previous study funded by the U.S. Army found that repetitive exposure to low-level sarin nerve gas caused changes in cholinergic receptors in lab rats.

New study finds daily drinking is biggest risk factor in serious liver disease

Long-term daily drinking, rather than weekly binge drinking, is by far the biggest risk factor in serious liver disease, according to a new report from the University of Southampton. The study, published in Addiction journal this week, concludes that increases in UK liver deaths are a result of daily or near daily heavy drinking, not episodic or binge drinking, and this regular drinking pattern is often discernable at an early age. It also reccommends that several alcohol-free days a week is a healthier drinking pattern. In the study of drinking patterns, dependency and lifetime drinking history in 234 subjects with liver disease, 106 had ALD (Alcohol-related Liver Disease) – 80 of whom had evidence of cirrhosis or progressive fibrosis – the team found that 71 per cent of ALD patients drank on a daily basis. In contrast to the patients with alcohol-related cirrhosis or fibrosis, patients with other forms of liver disease tended to drink sparingly with only 10 subjects (8 per cent) drinking moderately on four or more days each week. The study also explored lifetime drinking histories of 105 subjects and found that ALD patients started drinking at a significantly younger age (on average at 15 years old) than other subjects and had significantly more drinking days and units than non-ALD patients from the age of 20 onwards. Lead author of the study Dr Nick Sheron, consultant hepatologist and senior lecturer at the University of Southampton, comments: "If we are to turn the tide of liver deaths, then along with an overall reduction in alcohol consumption – which means tackling cheap booze and unregulated marketing – we need to find a way to identify those people who are most likely to develop alcohol-related illnesses at a much earlier stage, and perhaps we need to pay as much attention to the frequency of drinking occasions as we do to binge drinking. "The transition from a late teenage and early 20's binge drinking pattern to a more frequent pattern of increased intake may prove to be a useful point of intervention in the future, and the importance of three alcohol-free days each week should receive more prominence."

Mayo Clinic study suggests those who have chronic pain may need to assess vitamin D status

Mayo Clinic research shows a correlation between inadequate vitamin D levels and the amount of narcotic medication taken by patients who have chronic pain. This correlation is an important finding as researchers discover new ways to treat chronic pain. According to the Centers for Disease Control and Prevention, chronic pain is the leading cause of disability in the United States. These patients often end up taking narcotic-type pain medication such as morphine, fentanyl or oxycodone. This study found that patients who required narcotic pain medication, and who also had inadequate levels of vitamin D, were taking much higher doses of pain medication — nearly twice as much — as those who had adequate levels. Similarly, these patients self-reported worse physical functioning and worse overall health perception. In addition, a correlation was noted between increasing body mass index (a measure of obesity) and decreasing levels of vitamin D. Study results were published in a recent edition of Pain Medicine. "This is an important finding as we continue to investigate the causes of chronic pain," says Michael Turner, M.D., a physical medicine and rehabilitation physician at Mayo Clinic and lead author of the study. "Vitamin D is known to promote both bone and muscle strength. Conversely, deficiency is an under-recognized source of diffuse pain and impaired neuromuscular functioning. By recognizing it, physicians can significantly improve their patients' pain, function and quality of life." Researchers retrospectively studied 267 chronic pain patients admitted to the Mayo Comprehensive Pain Rehabilitation Center in Rochester from February to December 2006. Vitamin D levels at the time of admission were compared to other parameters such as the amount and duration of narcotic pain medication usage; self-reported levels of pain, emotional distress, physical functioning and health perception; and demographic information such as gender, age, diagnosis and body mass index. Further research should document the effects of correcting deficient levels among these patients, researchers recommend. This study has important implications for both chronic pain patients and physicians. "Though preliminary, these results suggest that patients who suffer from chronic, diffuse pain and are on narcotics should consider getting their vitamin D levels checked. Inadequate levels may play a role in creating or sustaining their pain," says Dr. Turner."Physicians who care for patients with chronic, diffuse pain that seems musculoskeletal — and involves many areas of tenderness to palpation — should strongly consider checking a vitamin D level," he says. "For example, many patients who have been labeled with fibromyalgia are, in fact, suffering from symptomatic vitamin D inadequacy. Vigilance is especially required when risk factors are present such as obesity, darker pigmented skin or limited exposure to sunlight." Assessment and treatment are relatively simple and inexpensive. Levels can be assessed by a simple blood test (25-hydroxyvitamin D [25(OH)D]). Under the guidance of a physician, an appropriate repletion regimen can then be devised. Because it is a natural substance and not a drug, vitamin D is readily available and inexpensive. In addition to the benefits of strong muscles and bones, emerging research demonstrates that vitamin D plays important roles in the immune system, helps fight inflammation and helps fights certain types of cancer.

To Fight Drug Addiction, UB Researchers Target the Brain with Nanoparticles

A precise, new nanotechnology treatment for drug addiction may be on the horizon as the result of research conducted at the University at Buffalo. Scientists in UB's Institute for Lasers, Photonics and Biophotonics and UB's Department of Medicine have developed a stable nanoparticle that delivers short RNA molecules in the brain to "silence" or turn off a gene that plays a critical role in many kinds of drug addiction. The UB team's in vitro findings were published online the week of March 23 in the Proceedings of the National Academy of Sciences. "These findings mean that in the future, we might be able to add a powerful pharmaceutical agent to the current arsenal of weapons in order to more effectively fight a whole range of substance addictions," said Paras N. Prasad, Ph.D., executive director of the UB Institute for Lasers, Photonics and Biophotonics and SUNY Distinguished Professor in the departments of Chemistry, Physics, Electrical Engineering and Medicine, who led the UB team.

Diabetics on high-fiber diets might need extra calcium

The amount of calcium your body absorbs might depend, in part, on the amount of dietary fiber you consume. Researchers at UT Southwestern Medical Center report that patients with noninsulin-dependent diabetes (type 2) excreted less calcium through their urine when they consumed 50 grams of fiber a day than when they ate 24 grams a day. Excreting less calcium indicates that they absorbed less of the mineral. “We already know that fiber helps improve your cholesterol and glucose control and improves your bowel regularity. Our new findings suggest that dietary fiber reduces the body’s capacity to absorb calcium,” said Dr. Abhimanyu Garg, professor of internal medicine and an investigator in the Center for Human Nutrition at UT Southwestern. He is senior author of a study appearing online in Diabetes Care. “Because more calcium equals better bone health, we recommend that people on high-fiber diets talk to their physician about increasing their dietary calcium as well, in order to get the most benefit from both.”

Researchers Studying Hearing Loss in Adult Animals Find that Auditory Regions of the Brain Convert to the Sense of Touch

Virginia Commonwealth University School of Medicine researchers have discovered that adult animals with hearing loss actually re-route the sense of touch into the hearing parts of the brain. In the study, published online in the Early Edition of the Proceedings of the National Academy of Sciences the week of March 23, the team reported a phenomenon known as cross-modal plasticity in the auditory system of adult animals. Cross-modal plasticity refers to the replacement of a damaged sensory system by one of the remaining ones. In this case, the sense of hearing is replaced with touch. About 15 percent of American adults suffer from some form of hearing impairment, which can significantly impact quality of life, especially in the elderly. “One often learns, anecdotally, that ‘grandpa’ simply turned off his hearing aid because it was confusing and no longer helped. Our study indicates that hearing deficits in adult animals result in a conversion of their brain’s sound processing centers to respond to another sensory modality, making the interpretation of residual hearing even more difficult,” said principal investigator Alex Meredith, Ph.D., a professor in the VCU Department of Anatomy and Neurobiology. “Whether this becomes a positive feedback cycle of increasing hearing difficulty is currently under investigation, but these findings raise the possibility that even mild hearing loss in adult humans can have serious and perhaps progressive consequences,” Meredith said.

Smithsonian scientist warns that palm oil development may threaten Amazon

Oil palm cultivation is a significant driver of tropical forest destruction across Southeast Asia. It could easily become a threat to the Amazon rainforest because of a proposed change in Brazil's legislation, new infrastructure and the influence of foreign agro-industrial firms in the region, according to William F. Laurance, senior scientist at the Smithsonian Tropical Research Institute in Panama. Laurance and Rhett A. Butler, founder of environmental science Web site Mongabay.com, warn in the open-access journal Tropical Conservation Science, that oil palm expansion in the Brazilian Amazon is likely to occur at the expense of natural forest as a result of a proposed revision to the forest code that requires landowners to retain 80 percent forest on lands in the Amazon. The new law would allow up to 30 percent of this reserve to consist of oil palm.
Expansion may be driven by economics. As the world's highest-yielding oil-containing seed source, oil palm is likely to offer better financial returns and to employ larger numbers of people than cattle ranching and mechanized soy farming, the dominant agricultural activities in Brazilian Amazon. Furthermore, oil palm producers will benefit from a "logging subsidy," whereby timber harvested from a tract of land helps to offset the cost of establishing a plantation. Before the recent run-up in palm oil prices, logging had been a factor in the profitability of oil palm plantations in Southeast Asia.

Long-term L-carnitine supplementation prevents development of liver cancer

A study will be published on March 21, 2009 in World Journal of Gastroenterology addresses the question. A research group in King Saud University, Kingdom of Saudi Arabia investigated, for the first time, the role of carnitine, a naturally occurring compound that is synthesized mainly in the liver, during the development of hepatocarcinogenesis. Authors of the study reported that carnitine deficiency is a risk factor and should be viewed as a mechanism in hepatic carcinogenesis, and that long-term L-carnitine supplementation prevents the development of liver cancer. Therefore, carnitine supplementation alone or in combination with other natural chemopreventive compounds could be used to prevent, slow or reverse the occurrence of liver cancer. Chemoprevention is defined as the use of naturally occurring and/or synthetic compounds in cancer therapy in which the occurrence of cancer can be entirely prevented, slowed or reversed. L-carnitine is a naturally occurring compound which is primarily located in mitochondria and possesses potential protective effects against many mitochondrial toxic agents. It is derived from two sources; endogenous synthesis, in the liver and kidney, and from exogenous dietary sources such as red meat and dairy products. L-carnitine is an essential cofactor for the translocation of long chain fatty acids from the cytoplasmic compartment into mitochondria, where beta-oxidation enzymes are located for ATP production. Despite the liver being the main organ responsible for endogenous synthesis of L-carnitine, we were unable to find any studies investigating the role of long-term endogenous carnitine depletion and/or carnitine deficiency during induction of hepatic carcinogenesis. The research team by Professor Sayed-Ahmed from College of Pharmacy, King Saud University used an experimental model of hepatocarcinogenesis under conditions of carnitine depletion and carnitine supplementation. In the carnitine-depleted rat model, there were a progressive increase in the activities of liver enzymes as well as massive degenerative changes and evidence of pre-neoplastic lesions in liver tissues including clusters of hepatocytes with atypia and an increased proliferative rate, diffuse bridging fibrosis and nodule formation, bile ducts with marked reactive atypia showing nuclear enlargement, high nuclear/cytoplasmic ratio and prominent nucleoli. Interestingly, L-carnitine supplementation resulted in a complete reversal of the increase in liver enzymes compared to normal values, as well as normal liver histology with unremarkable central vein and no evidence of pre-neoplastic lesions in liver tissues. Due to the fact that liver cancer is one of the major health problems in the world and a large sector of patients seek medical attention at a relatively late stage which increases the cost of treatment, King Saud University granted Prof. Sayed-Ahmed and his colleagues a research project with the following specific aims: (1) to understand the possible molecular mechanisms whereby carnitine deficiency provokes hepatic carcinogenesis. (2) to understand the relationship between hepatic cancer and its resistance to cancer chemotherapy, and (3) to gain knowledge on the possible mechanisms by which carnitine supplementation alone or in combination with other natural chemopreventive compounds could be used to prevent, slow or reverse the occurrence of liver cancer.

tTGA - Is it more essential in diagnosis of gluten sensitive enteropathy?

CD is a highly prevalent disease (1:100 to 1:300) which fulfils most of the criteria favoring mass screening. Despite this, screening for gluten sensitive enteropathy (GSE) is still controversial due to its dubious benefits and the acceptance of a gluten-free diet (GFD). A research article to be published on March 21, 2009 in the World Journal of Gastroenterology address this question. The study shows that GSE patients in the general population may not be identified by clinical features, since a similar percentage of related CD symptoms was found in individuals with positive and negative markers. This fact explains why CD remains underdiagnosed in a high proportion of affected subjects and is an additional argument for mass-screening using other approaches. It was also demonstarted that Marsh I subjects detected by t-TGA evaluation in a non-at-risk group for CD, were as symptomathic as Marsh III patients and also responded to GFD, reinforcing the final diagnosis of GSE in mild enteropathy. GSE in the general population is frequent and is clinically relevant, irrespective of the severity of the histological lesions. Mass screening programs are useful to identify these patients in order to initiate either a GFD or close follow-up monitoring. t-TG antibody is more sensitive than EmA for the diagnosis of the whole spectrum of GSE in the general population. The authors of the paper work in a tertiary hospital and individuals were recruited from an Occupational Health Department.

Intensive insulin therapy risks

Intensive insulin therapy significantly increases the risk of hypoglycemia in critically ill patients, found a new study in CMAJ (http://www.cmaj.ca/press/cmaj.090206.pdf). Intensive insulin therapy is used in many intensive care units around the world as a means to tightly regulate blood sugar. Although labour intensive, it has been recommended as a standard of care for critically ill patients by many organizations including the American Diabetes Association and the American Association of Clinical Endocrinologists. A randomized trial in 2001 reported that intensive insulin therapy significantly reduced hospital mortality, although subsequent trials have reported inconsistent effects on mortality and higher rates of severe hypoglycemia. The CMAJ study includes data from 26 trials, including the NICE-SUGAR Study on intensive insulin therapy, an international, multicentre randomized trial that is the largest intensive insulin therapy trial to date. The NICE-SUGAR study is published online in the New England Journal of Medicine March 24, 2009 and March 26 for the print edition. "By including the largest trial on intensive insulin therapy published to date, we provide the most current and precise estimate of the effect of intensive insulin therapy on vital status and hypoglycemia in the ICU setting," write Dr. Donald Griesdale, anesthesiologist and critical care physician at Vancouver General Hospital and clinical instructor at the University of British Columbia, and coauthors.
The CMAJ study looked at 26 trials involving 13 567 patients. There was a 6-fold increased risk of hypoglycemia compared to the control treatment. The study was conducted by researchers from the University of British Columbia and Vancouver General Hospital, Vancouver, BC; Harvard School of Public Health, Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, Boston, Mass; Queen's University and Kingston General Hospital, Kingston, Ontario; McMaster University, Hamilton, Ontario; Royal North Shore Hospital and the University of Sydney, Australia.

Mayo researchers find link between anesthesia exposure and learning disabilities in children

Mayo Clinic researchers have found that children who require multiple surgeries under anesthesia during their first three years of life are at higher risk of developing learning disabilities later. Several studies have suggested that anesthetic drugs may cause abnormalities in the brains of young animals. This is the first study in humans to suggest that exposure of children to anesthesia may have similar consequences. The finding is reported in the current issue of the journal Anesthesiology. Using data from the long-term Rochester Epidemiology Project, researchers studied the medical records of 5,357 children from Olmsted County who were born between 1976 and 1982. The research team, led by Robert Wilder, M.D., Ph.D., a Mayo Clinic anesthesiologist, found that although one exposure to anesthesia was not harmful, more than one almost doubled the risk that a child would be identified as having a learning disability before age 19. The risk also increased with longer durations of anesthesia. "It's very important for parents and families to understand that although we see a clear difference in the frequency of learning disabilities in children exposed to anesthesia, we don't know whether these differences are actually caused by anesthesia," says Randall Flick, M.D., a Mayo Clinic anesthesiologist and co-author of the study. "The problem is that anyone who underwent an anesthetic also had surgery," says Dr. Wilder. "It's unclear whether it's the anesthetic, the physiological stress of surgery or perhaps the medical problems that made surgery necessary that are responsible for the learning disabilities." Young children's brains are more vulnerable to a variety of problems because they are undergoing dynamic growth. The brain is rapidly forming connections between cells and trimming excess cells and connections, says Dr. Wilder. The general anesthesia chemicals in use during the study period were primarily halothane and nitrous oxide (laughing gas). Although halothane is no longer used in the U.S., it has been replaced by newer agents that have similar effects on the brain. Nitrous oxide is widely used throughout the U.S. and the world.

Caltech researchers find tiny genetic change keeps nicotine from binding to muscle cells

A tiny genetic mutation is the key to understanding why nicotine--which binds to brain receptors with such addictive potency--is virtually powerless in muscle cells that are studded with the same type of receptor. That's according to California Institute of Technology (Caltech) researchers, who report their findings in the March 26 issue of the journal Nature. By all rights, nicotine ought to paralyze or even kill us, explains Dennis Dougherty, the George Grant Hoag Professor of Chemistry at Caltech and one of the leaders of the research team. After all, the receptor it binds to in the brain's neurons--a type of acetylcholine receptor, which also binds the neurotransmitter acetylcholine--is found in large numbers in muscle cells. Were nicotine to bind with those cells, it would cause muscles to contract with such force that the response would likely prove lethal. Obviously, considering the data on smoking, that is not what happens. The question has long been: Why not? "It's a chemical mystery," Dougherty admits. "We knew something subtle had to be going on here, but we didn't know exactly what." That subtlety, it turns out, lies in the slight tweaking of the structure of the acetylcholine receptor in muscle cells versus its structure in brain cells. The shape of the acetylcholine receptor, and the way the chemicals that bind with it contort themselves to fit into that receptor, is determined by a number of different weak chemical interactions. Perhaps most important is an interaction that Dougherty calls "underappreciated"--the cation-? interaction, in which a positively charged ion and an electron-rich ? system come together. Back in the late 1990s, Dougherty and colleagues had shown that the cation-? interaction is indeed a key part of acetylcholine's ability to bind to the acetylcholine receptors in muscles. "We assumed that nicotine's charge would cause it to do the same thing, to have the same sort of strong interaction that acetylcholine has," says Dougherty. "But we found that it didn't." This would explain why smoking doesn't paralyze us; if the nicotine can't get into the muscle's acetylcholine receptors, it can't cause the muscles to contract.

Columbia researchers identify early brain marker for familial form of depression

Findings from one of the largest-ever imaging studies of depression indicate that a structural difference in the brain – a thinning of the right hemisphere – appears to be linked to a higher risk for depression, according to new research at Columbia University Medical Center and the New York State Psychiatric Institute. The research was led by Myrna Weissman, Ph.D., professor of epidemiology in psychiatry, Columbia University College of Physicians and Surgeons, and director of the Division of Epidemiology at the New York State Psychiatric Institute, and co-senior author of the study, and Bradley Peterson, M.D., director of Child & Adolescent Psychiatry and director of MRI Research in the Department of Psychiatry at Columbia University Medical Center and the New York State Psychiatric Institute, and first author of the study. Published in the upcoming early online edition of the Proceedings of the National Academy of Sciences (PNAS), the researchers found that people at high risk of developing depression had a 28 percent thinning of the right cortex, the brain's outermost surface, compared to people with no known risk. The drastic reduction surprised researchers, which they say is on par with the loss of brain matter typically observed in persons with Alzheimer's disease and schizophrenia. "The difference was so great that at first we almost didn't believe it. But we checked and re-checked all of our data, and we looked for all possible alternative explanations, and still the difference was there," said Dr. Peterson. Dr. Peterson says the thinner cortex may increase the risk of developing depression by disrupting a person's ability to pay attention to, and interpret, social and emotional cues from other people. Additional tests measured each person's level of inattention to and memory for such cues. The less brain material a person had in the right cortex, the worse they performed on the attention and memory tests. The study compared the thickness of the cortex by imaging the brains of 131 subjects, aged 6 to 54 years-old, with and without a family history of depression. Structural differences were observed in the biological offspring of depressed subjects but were not found in the biological offspring of those who were not depressed. One of the goals of the study was to determine whether structural abnormalities in the brain predispose people to depression or are a cause of the illness. Dr. Peterson said, "Because previous biological studies only focused on a relatively small number of individuals who already suffered from depression, their findings were unable to tease out whether those differences represented the causes of depressive illness, or a consequence." The study found that thinning on the right side of brain did not correlate with actual depression, only an increased risk for the illness. It was subjects who exhibited an additional reduction in brain matter on the left side, who went on to develop depression or anxiety. "Our findings suggest rather strongly that if you have thinning in the right hemisphere of the brain, you may be predisposed to depression and may also have some cognitive and inattention issues. The more thinning you have, the greater the cognitive problems. If you have additional thinning in the same region of the left hemisphere, that seems to tip you over from having a vulnerability to developing symptoms of an overt illness," said Dr. Peterson.

Experimental Parkinson's therapy may have robust weight-loss effect

A growth factor used in clinical experiments to rescue dying brain cells in Parkinson patients may cause unwanted weight loss if delivered to specific areas of the brain, according to University of Florida researchers in the March online edition of Molecular Therapy. The discovery is a cautionary warning for experimental treatments to treat Parkinson's disease that use GDNF, short for glial cell line-derived neurotrophic factor. In addition, the finding broadens understanding of the brain's role in the regulation of metabolism and body weight, suggesting that gene therapy techniques in the brain potentially could control obesity. "People shouldn't interpret our result to mean this is a terrible side effect that precludes ability to do GDNF gene therapy for Parkinson's disease, but it does show that it is extremely important to place the therapy in the correct brain region," said Ron Mandel, a professor of neuroscience at UF's McKnight Brain Institute and the Powell Gene Therapy Center. "The good news for Parkinson's patients is that the finding doesn't discredit the current target." Parkinson's disease affects between 500,000 and 1.5 million Americans, causing patients to gradually develop movement problems, including tremors, stiffness and slowness of movement. Current treatments only address symptoms and do nothing to slow the disease's progression, which is caused by degeneration and death of nerve cells that produce dopamine, a substance necessary for communication between cells that coordinate movement. GDNF rescues the dopamine-producing cells in cell cultures and animal models of Parkinson's disease. But Parkinson patients were disappointed in September 2004 when the biotechnology company Amgen discontinued a clinical trial using GDNF because of concerns about safety and effectiveness. The therapy was delivered through surgically implanted catheters to a region called the putamen, and several patients said their physical conditions and quality of life improved. A different approach in a more recent trial by the biopharmaceutical company Ceregene involved gene therapy, in which the gene to produce neurturin, a sister protein to GDNF, was transferred into the putamen region of Parkinson patients. But it showed no marked effectiveness.

Gene variants may determine lung function and susceptibility to maternal smoking

A tiny variation within a single gene can determine not only how quickly and well lungs grow and function in children and adolescents, but how susceptible those children will be to exposure to second-hand tobacco smoke, even in utero, according to researchers from the University of Southern California. "Many factors can affect lung function and growth, including genetic variation and environmental exposures such as tobacco smoke and air pollutants," said Carrie Breton, Sc.D., lead author of the study conducted at the University of Southern California. "We wanted to determine whether specific gene variations would have measurable and predictable effects on lung function growth and susceptibility to environmental insults. We looked at a class of genes known to be involved in antioxidant defense, the glutathione-s transferase (GST) genes. Overall, we found that variation in several of the GST genes was important. This was particularly true for children of mothers who had smoked during pregnancy." The researchers analyzed eight years' worth of lung function metrics and genotyping data from more than 2,100 children from two cohorts of fourth-graders. The lung function measurements used were maximal mid expiratory flow rate (MMEF), forced vital capacity (FVC) and forced expiratory volume in one second (FEV1). "FEV1 is a measure of large airways, FVC of total lung volume and MMEF of smaller airways, so they measure slightly different things and we wouldn't necessarily expect to see all outcomes behaving the same," said Dr. Breton. They found that for three of the specific haplotypes (patterns of genetic variation within genes) they investigated, each had a significant effect on lung function.

Nutritious new low-sugar juice targeted for diabetics, individuals with high blood sugar

Scientists in China are reporting development of a low-calorie, low-sugar vegetable juice custom-designed for millions of individuals with diabetes and pre-diabetic conditions that involve abnormally high blood sugar. They reported on the new drink here at the 237th National Meeting of the American Chemical Society. Heqin Xing, Ph.D., and Xiuqi Liu of Jilin University in Changchun, China, described a cost-effective method of preparing a special type of vegetable drink using lactic acid-producing bacteria (LAB) to remove carbohydrates while retaining good taste, vitamins and other nutrients. "This is an exciting development," Liu said. "The process significantly removes sugar but retains the nutritional content of the juice's raw materials." To develop the juice — made from pumpkin, balsam pear, onion and carrots — Xing and Liu turned to an age-old technique in the art of food production. For thousands of years, people have cultured food — including everyday eats such as yogurt, cheeses and sausage — by using the same LAB.LAB microbes produce a compound commonly found in sour milk products called lactic acid. Because of LAB's healthy link to food production, this class of bacteria is also referred to as probiotics. In the study, LAB reduced sugar content of the vegetable juice by transforming carbohydrates into lactic acid by a routine conversion process called fermentation. As this process increases the juice's acidity, it extends its shelf life as it inhibits growth of other bacteria. Compared to other microorganisms, LAB are known for their ability to withstand acidic environments. In addition to the lactic acid's protection against contamination, the acidity from fermentation could enhance flavors in the beverage.

EPA new strategic plan for evaluating the toxicity of chemicals

EPA is releasing a new approach to advance the science upon which the agency bases its regulatory decisions and policies, resulting in better protection for human health and the environment. Today, EPA released the "U.S. Environmental Protection Agency's Strategic Plan for Evaluating the Toxicity of Chemicals." This strategic plan outlines a new scientific approach that will allow EPA to assess risks from many chemicals and mixtures by adopting new toxicity testing methods that use recent advances in molecular biology, genomics, and computational sciences. When fully implemented, EPA will be able to screen thousands of environmental chemicals quickly for potentially harmful effects. The strategic plan will also allow EPA scientists to look at how children may react differently to the same chemicals as adults, thus providing better health protection for children.

Bad news for insomniacs - 'hunger hormones' affected by poor sleep

Insomnia has long been associated with poor health, including weight gain and even obesity. Now researchers at UCLA have found out why. In a study to be published in the May issue of the journal Psychoneuroendocrinology and currently available online by subscription, Sarosh Motivala, an assistant professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA, and colleagues looked at two hormones that are primarily responsible for regulating the body's energy balance, telling the body when it is hungry and when it is full. The study found that chronic insomnia disrupts one of these two hormones. To date, no study has evaluated nocturnal levels of the two hormones, ghrelin and leptin, in primary insomnia patients. Ghrelin, a peptide secreted by the stomach, stimulates appetite and increases before meals. Leptin, which affects body weight and is secreted primarily by fat cells, signals the hypothalamus regarding the degree of fat storage in the body; decreased leptin tells the body there is a calorie shortage and promotes hunger, while increased levels promote energy expenditure. In the study, researchers compared healthy sleepers with those suffering from chronic insomnia and measured the levels of the two hormones at various times throughout the night. They found that while leptin levels averaged out over the night to be roughly the same between the two groups, levels of ghrelin were 30 percent lower in insomnia sufferers. On the face of it, a decreased level of ghrelin would seem to inhibit weight gain; it is an increase in ghrelin, after all, that stimulates appetite. But Motivala compared his findings with other, earlier studies on sleep deprivation and speculates that a switch may occur during the day: Sleep loss leads to increased ghrelin and decreased leptin, a "double whammy" that stimulates appetite. Motivala is currently working on a study to examine this switch.

Concern over inappropriate diagnosis and treatment of thyroid problems

More and more people are being inappropriately diagnosed and treated for underactivity of the thyroid gland (known as primary hypothyroidism), warn doctors in an editorial published on bmj.com today. Hypothyroidism is caused by insufficient production of thyroid hormone by the thyroid gland. It affects about three per cent of the population and is usually treated in primary care. Blood tests are essential in confirming the diagnosis of hypothyroidism. But doctors at the British Thyroid Association are concerned that, in recent years, increasing numbers of patients with and without confirmed thyroid disease have been diagnosed and treated inappropriately with thyroid hormones. "This is potentially an enormous problem, given that in any one year one in four people in the United Kingdom have their thyroid function checked," they warn. The Royal College of Physicians recently set out clear guidance for the diagnosis and treatment of primary hypothyroidism in the United Kingdom, so why have these problems arisen, ask the authors?
Hypothyroidism is common and is becoming more prevalent because of increased life expectancy and an ageing population, they explain. Thyroid hormones also affect most organs, so hypothyroidism presents with symptoms that can mimic other conditions. This can lead to an incorrect diagnosis which could expose some patients to the harmful effects of excess thyroid hormones, while other serious conditions may go undiagnosed. Information available on the internet and media interest in alternative modes of diagnosis and treatment of hypothyroidism, have also caused an increase in requests for inappropriate investigations and non-standard treatments, as well as referrals to non-accredited practitioners, they add.

Drinking very hot tea can increase the risk of throat cancer

People are advised to wait a few minutes before drinking a cup of freshly-boiled tea today as a new study, published on bmj.com, finds that drinking very hot tea (70°C or more) can increase the risk of cancer of the oesophagus, the muscular tube that carries food from the throat to the stomach. The study was carried out in northern Iran, where large amounts of hot tea are drunk every day. But an accompanying editorial says these findings are not cause for alarm and the general advice is to allow foods and beverages to cool a little before swallowing. Cancers of the oesophagus kill more than 500,000 people worldwide each year and oesophageal squamous cell carcinoma (OSCC) is the commonest type. In Europe and America, it is mainly caused by tobacco and alcohol use and is more common in men than in women, but drinking hot beverages is also thought to be a risk factor. Golestan Province in northern Iran has one of the highest rates of OSCC in the world, but rates of smoking and alcohol consumption are low and women are as likely to have a diagnosis as men. Tea drinking, however, is widespread, so researchers set out to investigate a possible link between tea drinking habits and risk of OSCC. They studied tea drinking habits among 300 people diagnosed with OSCC and a matched group of 571 healthy controls from the same area. Nearly all participants drank black tea regularly, with an average volume consumed of over one litre a day. Compared with drinking warm or lukewarm tea (65°C or less), drinking hot tea (65-69°C) was associated with twice the risk of oesophageal cancer, and drinking very hot tea (70°C or more) was associated with eight-fold increased risk.

Pregnant women who smoke, urged to give up before 15-week 'deadline'

Women who stop smoking before week 15 of pregnancy cut their risk of spontaneous premature birth and having small babies to the same as non-smokers, according to research published on bmj.com today.
Women who do not quit by 15 weeks, are three times more likely to give birth prematurely and twice as likely to have small babies compared to women who have stopped smoking, say the researchers. The lead author, Dr Lesley McCowan at the University of Auckland, says that maternity care providers need to emphasise to women the major benefits of giving up smoking before 15 weeks in pregnancy with the goal of becoming smoke free as early in pregnancy as possible. While it is well established that smoking in pregnancy increases the risk of miscarriage, ectopic pregnancy, premature birth, small babies, stillbirth and neonatal death, say the authors, no study has yet determined whether stopping smoking in early pregnancy reduces the risks of small babies and premature births. The authors surveyed over 2,500 pregnant women participating in the SCOPE study in Australia and New Zealand at 15 weeks gestation. The participants were divided into three groups: non smoker, stopped smoker and current smoker. The 'stopped smoker' group all gave up before 15 weeks of pregnancy.The results show that there were no differences between the rates of premature birth between stopped smokers and non-smokers, whereas current smokers had much higher risk. Similar results were revealed for expected baby size. Another important finding was that women who stopped smoking were not more stressed than women who continued to smoke.

Difference in fat storage may explain lower rate of liver disease in African-Americans

Where different ethnic groups store fat in their bodies may account for differences in the likelihood they'll develop insulin resistance and non-alcoholic fatty liver disease, researchers at UT Southwestern Medical Center have found. According to research reported in the online edition and the March issue of Hepatology, African-Americans with insulin resistance might harbor factors that protect them from this form of metabolic liver disease. Despite similarly high rates of associated risk factors such as insulin resistance, obesity and diabetes among African-Americans and Hispanics, African-Americans are less likely than Hispanics to develop non-alcoholic fatty liver disease, or NAFLD. The disease is characterized by high levels of triglycerides in the liver and affects as many as one-third of American adults. "If we can identify the factors that protect African-Americans from this liver disease, we may be able to extrapolate those to other populations and perhaps develop targeted therapies to help populations prone to NAFLD," said Dr. Jeffrey Browning, assistant professor of internal medicine in the UT Southwestern Advanced Imaging Research Center and the study's senior author. Previous research has shown that when African-Americans do develop NAFLD, they're less likely to reach the later stages of liver disease. Prior work by Dr. Browning and other UT Southwestern scientists has revealed that NAFLD is more prevalent among Hispanics than African-Americans or Caucasians. For the current study, Dr. Browning and his colleagues analyzed data gathered in the multi-ethnic, population-based Dallas Heart Study. Starting in the year 2000, more than 2,100 participants provided blood samples and underwent multiple body scans with magnetic resonance imaging and computed tomography to examine the liver, heart and other organs. Body composition, including fat distribution, also was scrutinized. The study found that African-Americans and Hispanics both have obesity rates of about 48 percent among their respective populations, as well as diabetes rates of about 21 percent. Only 23 percent of African-Americans, however, have NAFLD, compared with 45 percent of Hispanics. Similarly, African-Americans are less likely to have high levels of triglycerides and abdominal fat – both characteristics of insulin resistance – when compared with Hispanics or Caucasians, even though overall rates of insulin resistance among all groups are the same, researchers found.

Targeting oxidized cysteine through diet could reduce inflammation and lower disease risk

A team of scientists at Emory University School of Medicine has identified a direct link between oxidative stress and inflammatory signals in the blood. The finding could lead to improved strategies for preventing several diseases by including antioxidants in the diet and for reducing the impact of inflammation in critically ill patients by adding cysteine to intravenous or tube feeding. Many normal metabolic functions produce reactive forms of oxygen that can damage cells. Oxidative stress, a disruption of the body's ability to control reactive forms of oxygen, has been connected with heart disease, diabetes and several neurodegenerative diseases. However, scientists are still learning about the best ways to measure and reduce oxidative stress, says Dean P. Jones, PhD, professor of medicine and director of the Clinical Biomarkers Laboratory at Emory University School of Medicine. For example, large-scale clinical trials have shown little benefit in supplementing the diet with antioxidants such as vitamins C and E.Jones and his colleagues, including Thomas R. Ziegler, MD of the Emory Department of Medicine, have been concentrating on a measure of oxidative stress in the blood: cysteine, an amino acid found in most proteins in the body. Cysteine can exist in two forms: oxidized and reduced. The higher the level of oxidative stress outside the cell, the more oxidized cysteine there is. Other indicators such as glutathione are more important inside cells. Several studies have shown that levels of oxidized cysteine in the blood tend to rise as people age. Smoking and alcohol consumption are also linked with higher levels of oxidized cysteine. In addition, Jones and Ziegler have found that critical illness and malnutrition are associated with oxidative stress and oxidized cysteine in the blood. Working with Jones, graduate student Smita Iyer and immunologist Mauricio Rojas, MD, found that a high level of oxidized cysteine drives white blood cells to send out inflammatory messages in the form of the protein IL-1 beta.

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