Pulmonary hypertension is a rare but serious and often fatal disease.  The most commonly prescribed medication for pulmonary hypertension is epoprostenol given daily by intravenous infusion.  However, even on therapy, many patients do poorly.  Researchers conducted an open-label randomized study of 267 patients to determine whether a combination of sildenafil (Viagra) and epoprostenol could improve outcomes more than epoprostenol alone.  All of the patients in the study had been receiving intravenous epoprostenol for at least three months, and were randomly assigned either oral sildenafil or placebo for 16 weeks.  At the end of the study, patients given sildenafil could walk longer distances and had a longer period of time before getting worse than those given placebo.  Researchers concluded that adding sildenafil to epoprostenol therapy may improve some outcomes for patients with pulmonary hypertension.

Recent studies indicate that infusing hearts with stem cells taken from bone marrow could improve cardiac function after myocardial infarction (tissue damage that results from a heart attack).  But in a recent systematic review, Cochrane Researchers concluded that more clinical trials are needed to assess the effectiveness of stem cell therapies for heart patients, as well as studies to establish how these treatments work.

In a heart attack, blocked arteries can cut off the blood supply to areas of heart tissue.  This leads to myocardial infarction severe tissue damage caused by lack of oxygen, which is transported in the blood.

“We need more studies that look at the long term effects of these interventions, as well as at the types of cells that are used and how they actually repair the heart tissue,” says lead researcher Dr. Enca Martin-Rendon, who works in the Stem Cell Research Department, NHS Blood and Transplant, at the John Radcliffe Hospital in Oxford, UK.

The team drew together data from 13 different trials involving 811 patients.  Although these trials show that treatment with bone marrow stem cells (BMSCs) may lead to a moderate improvement in cardiac function, the researchers say there is still not enough evidence to confirm this.  They also found that BMSC treatment did not reduce the measurable area of damaged heart tissue.

Only three trials looked to see if effects lasted for more than six months after BMSC treatment.  The researchers discovered that in these trials, there was no evidence of any benefit 12 months after treatment.

Quite how BMSCs cause this short term benefit is uncertain.  One theory is that they enable extra blood vessels to develop, while another is that they release chemicals that encourage the growth of healthy heart muscle cells while decreasing the development of scar tissue in the damaged area.

“If it turns out these treatments are beneficial in any way, they could be made available to all heart attack patients.  We think infusion with stem cells may help increase blood flow into damaged heart tissues, but without more investment in this area of research, we can’t be sure,” says Martin-Rendon.

An international team of researchers led by Professors Mark Caulfield and Patricia Munroe, from the William Harvey Research Institute at Barts and The London School of Medicine and Dentistry with Chris Cheeseman at the University of Alberta in Canada and Kelle Moley at the University of Washington in USA, have shown that the SLC2A9 gene, which encodes a glucose transporter, is also a high-capacity urate transporter, and thus possibly a new drug target for gout.  Their findings are published in this week’s PloS Medicine (7 October 2008).

Several urate transporters have already been identified but recently, using an approach called genome-wide association scanning, Caulfield and others found that some genetic variants of a human gene called SLC2A9 are more common in people with high serum urate levels than in people with normal levels.  SLC2A9 encodes a glucose transporter (a protein that helps to move the sugar glucose through cell membranes) and is highly expressed in the kidney’s main urate handling site.  Professor Caulfield and his team investigated the possibility that the protein made by the SLC2A9 gene might be a urate transporter and tested whether genetic variations in SLC2A9 might be responsible for the association between serum urate levels and high blood pressure.

The team first expressed SLC2A9 in frog eggs, a type of cell that does not have its own urate transporter.  They found that SLC2A9 transported urate about 50 times faster than glucose, and that glucose facilitated SLC2A9-mediated urate transport.  Similarly, over expression of SLC2A9 in human embryonic kidney cells more than doubled their urate uptake.  Conversely, when the researchers used a technique called RNA interference to reduce the expression of mouse SLC2A9 in mouse cells that normally makes this protein, urate transport was reduced.  Researchers then looked at two genetic variations within SLC2A9 that vary between individuals (so-called single polynucleotide polymorphisms) in nearly 900 men who had had their serum urate levels and urinary urate excretion rates measured.  They found that certain genetic variations at these two sites were associated with increased serum urate levels and decreased urinary urate excretion.  Finally, the researchers used a statistical technique called meta-analysis to look for an association between one of the SLC2A9 gene variants and blood pressure.  In two separate meta-analyses that together involved more than 20,000 participants in several studies, there was no association between this gene variant and blood pressure.

Overall, these findings indicate that SLCA9 is a high capacity urate transporter, and suggest that this protein plays an important part in controlling serum urate levels.  They provide confirmation that common genetic variants in SLC2A9 affect serum urate levels to a marked degree, although they do not show exactly which genetic variant is responsible for increasing serum urate levels.  They also provide important new insights into how the kidneys normally handle urate and suggest ways in which this essential process may sometimes go wrong.  The findings could eventually lead to new treatments for gout and possibly for other diseases that are associated with increased serum urate levels.

Professor Mark Caulfield said: “This MRC funded study shows how a team of international researchers can find a completely unsuspected mechanism for urate handling in the kidney.  Such discoveries could pave the way for new medicines.”

Reported in the Oct. 3, 2008 issue of Cell, the findings–from a study in mice–point to a completely new approach to treating and preventing obesity in humans.  The discovery also offers hope for new ways to treat related disorders, such as type 2 diabetes and cardiovascular diseases–the most prevalent health problems in the United States and the rest of the developed world.

Led by Dongsheng Cai, an assistant professor of physiology at the UW School of Medicine and Public Health, the researchers looked specifically at the hypothalamus–the brain structure responsible for maintaining a steady state in the body–and for the first time found that a cell-signaling pathway primarily associated with inflammation also influences the regulation of food intake.  Stimulating the pathway led the animals to increase their energy consumption, while suppressing it helped them maintain normal food intake and body weight.

The research stems from recent explorations into the problem called metabolic inflammation, a by-product of too much food or energy consumption.  Unlike the classical inflammation typically observed in infections, injuries and diseases such as cancer, the metabolic inflammation seen in obesity-related diseases is much milder, doesn’t lead to overt symptoms or cause tissues damage.

“Metabolic inflammation is a chronic, low-grade condition consisting of inflammatory-like responses at the molecular level.  It has many downstream consequences,” says Cai.  “It causes cellular dysfunction, which can decrease the regulation of several physiological processes, including metabolism.”

Scientists believe that metabolic inflammation may be at the core of many chronic, obesity-related metabolic disorders that are so common today, he adds.

Cai and his team zeroed in on NF-kappaB, a protein complex that can be activated specifically by IKKbeta to induce inflammatory reactions in many cell systems.

In earlier studies at Harvard, Cai and colleagues found that the pathway interrupted sugar, fat or protein metabolism in tissues where metabolism typically takes place–liver, fat and skeletal muscle.  Feeding mice high-sugar and high-fat diets activated the pathway in these tissues.

Once he arrived at the SMPH three years ago, Cai began to consider whether metabolic inflammation might affect “higher-up” players in the central nervous system, particularly the hypothalamus.  This brain structure is a critical master regulator of appetite and energy balance, and also controls metabolism in the peripheral tissues he had studied before.  But nobody knew how the hypothalamus might contribute to the development of metabolic diseases such as obesity and diabetes.

“We wanted to learn whether the pathway or pathways underlying metabolic inflamm ation could affect metabolism regulators in the central nervous system,” he says.

In the current study, Cai and his team found first that IKKbeta/NF-kappaB does indeed exist in specific neurons in the hypothalamus.  The pathway is much more abundant in the hypothalamus than in peripheral tissue, and it normally remains inactive in the brain.

The researchers next showed that over-nutrition through high-fat diet feeding activates IKKbeta/NF-kappaB, specifically in neurons in the hypothalamus.

“When we knocked out the IKKbeta gene to suppress NF-kappaB activity in these neurons, the animals were significantly protected from energy over-consumption and obesity development,” Cai says.

The researchers also examined a cell component called the endoplasmic reticulum (ER), shown recently to be involved in metabolic diseases involving over-nutrition, to see if it might play a role in linking over-nutrition to activate IKKbeta/NF-kappaB in the hypothalamus.

“At the intracellular level, when the ER is challenged with over-nutrition, this leads to ER stress, which can push the IKKbeta/NF-kappaB pathway to an active state, although the involved reactions could be quite complicated,” Cai says.

In several experiments, the researchers found that ER stress caused by over-nutrition activated IKKbeta/NF-kappaB in the hypothalamus.  Suppressing ER stress in the central nervous system significantly preserved normal regulation of food intake and prevented obesity.

Cai says there’s still a lot of work to be done.  His group has begun studying IKKbeta/NF-kappaB’s connections to other pathways and regulations in the hypothalamus.

“The ultimate goal will certainly be to identify a selective and effective suppressor of the pathway to target related neurons,” he says.

But Cai continues to look at the big picture, seeking answers to questions such as: “How does the environment connect to the genetics that seem to underlie the obesity epidemic?  What are the key steps that have led to the dramatic rise of diabetes in the past three decades?  And Why can’t the body adjust to changes that have occurred in the way people eat and what they eat?”

Higher levels of urinary Bisphenol A (BPA), a chemical compound commonly used in plastic packaging for food and beverages, is associated with cardiovascular disease, type 2 diabetes and liver-enzyme abnormalities, according to a study in the September 17 issue of JAMA. This study is being released early to coincide with a Food and Drug Administration (FDA) hearing on BPA.

BPA is one of the world’s highest production–volume chemicals, with more than two million metric tons produced worldwide in 2003 and annual increase in demand of 6 percent to 10 percent annually, according to background information in the article. It is used in plastics in many consumer products. “Widespread and continuous exposure to BPA, primarily through food but also through drinking water, dental sealants, dermal exposure, and inhalation of household dusts, is evident from the presence of detectable levels of BPA in more than 90 percent of the U.S. population,” the authors write. Evidence of adverse effects in animals has created concern over low-level chronic exposures in humans, but there is little data of sufficient statistical power to detect low-dose effects. This is the first study of associations with BPA levels in a large population, and it explores “normal” levels of BPA exposure.

David Melzer, M.B., Ph.D., of Peninsula Medical School, Exeter, U.K., and colleagues examined associations between urinary BPA concentrations and the health status of adults, using data from the National Health and Nutrition Examination Survey (NHANES) 2003-2004. The survey included 1,455 adults, age 18 through 74 years, with measured urinary BPA concentrations.

The researchers found that average BPA concentrations, adjusted for age and sex, appeared higher in those who reported diagnoses of cardiovascular diseases and diabetes. A 1-Standard Deviation (SD) increase in BPA concentration was associated with a 39 percent increased odds of cardiovascular disease (angina, coronary heart disease, or heart attack combined) and diabetes.

When dividing BPA concentrations into quartiles, participants in the highest BPA concentration quartile had nearly three times the odds of cardiovascular disease compared with those in the lowest quartile. Similarly, those in the highest BPA concentration quartile had 2.4 times the odds of diabetes compared with those in the lowest quartile.

In addition, higher BPA concentrations were associated with clinically abnormal concentrations for three liver enzymes. No associations with other diagnoses were observed.

“Using data representative of the adult U.S. population, we found that higher urinary concentrations of BPA were associated with an increased prevalence of cardiovascular disease, diabetes, and liver-enzyme abnormalities. These findings add to the evidence suggesting adverse effects of low-dose BPA in animals. Independent replication and follow-up studies are needed to confirm these findings and to provide evidence on whether the associations are causal,” the authors conclude. “Given the substantial negative effects on adult health that may be associated with increased BPA concentrations and also given the potential for reducing human exposure, our findings deserve scientific follow-up.”

Scientists have discovered a compound that could lead to new treatments for heart attacks as well as methods to protect hearts during open heart surgery and other situations in which blood flow to the heart is interrupted.In the process, the researchers uncovered cellular mechanisms that help explain how alcohol can protect against heart attack damage. In addition, they have uncovered a possible key to reducing chest pain and the heart attack damage among millions of people of East Asian descent who are genetically unable to respond to nitroglycerin and other cardiovascular treatments.

A research team of scientists at Stanford and Indiana universities schools of medicine reports in the Sept. 12 issue of the journal Science that by jump-starting a particular enzyme they were able to significantly reduce the amount of cell death caused by lack of blood flow to the heart.

The group, led by Daria Mochly-Rosen, Ph.D., professor of chemical and systems biology at Stanford, found that administering a compound called Alda-1 activated the enzyme, reducing heart muscle damage in experiments involving rats.

First, however, the researchers studied various mechanisms known to provide cardioprotection to heart muscle cells, including the use of ethanol, to better understand how those mechanisms worked. That work revealed a cellular signaling system that activated a particular enzyme called ALDH2.

“The idea was to find a small molecule that could bypass the signaling process and activate the enzyme directly,” said Thomas D. Hurley, Ph.D., professor of biochemistry and molecular biology and director of the Center for Structural Biology at the IU School of Medicine. Hurley’s research has included years of study of the ALDH2 enzyme.

Although the Alda-1 molecule reduced heart tissue damage in laboratory tests, years of work will be necessary to refine the compound into a version that would be potentially effective and safe for human use, Dr. Hurley said. That benefit could extend to about 40 percent of people of East Asian descent who carry a mutated form of the ALDH2 enzyme, which puts them at increased risk of cardiovascular damage.

Marauding molecules cause the tissue damage that underlies heart attacks, sunburn, Alzheimer’s and hangovers.  But scientists at the Stanford University School of Medicine say they may have found ways to combat the carnage after discovering an important cog in the body’s molecular detoxification machinery.

The culprit molecules are oxygen byproducts called free radicals.  These highly unstable molecules start chain reactions of cellular damage an escalating storm that ravages healthy tissue.

“We’ve found a totally new pathway for reducing the damage caused by free radicals, such as the damage that happens during a heart attack,” said Daria Mochly-Rosen, PhD, professor of chemical and systems biology and the senior author of a study reporting the new findings.  The research will appear in the Sept. 12 issue of Science.

Before the study, scientists knew that heart muscle could be preconditioned to resist heart attack damage for instance, moderate drinkers tend to have smaller, less severe heart attacks than teetotalers.  But scientists didn’t understand how pre-conditioning worked.

To figure out how alcohol protects heart muscle from free-radical damage, Mochly-Rosen’s team tested alcohol pretreatment in a rat heart-attack model.  They compared the enzymes activated during the attacks to those switched on with no alcohol.  Enzymes are the “doers” of the cellular machinery, catalyzing all of the biochemical reactions that form the basis of life.

Surprisingly, the treatment activated aldehyde dehydrogenase 2 (ALDH2), an obscure alcohol-processing enzyme.  Alcohol pretreatment increased the enzyme’s activity during heart attack by 20 percent, leading to a 27 percent drop in the associated damage.

“Although this enzyme was discovered a long time ago, my research group knew nothing about the enzyme except that it helps remove alcohol when people drink,” said Mochly-Rosen, who is also the senior associate dean for research in the School of Medicine and the George D. Smith Professor in Translational Medicine.

ALDH2 wasn’t one of the well-studied antioxidant players that the scientists expected to find fighting free-radical damage.  The enzyme neutralizes an aldehyde molecule, a toxic byproduct of the ethanol in alcoholic beverages.  But aldehydes are also formed in the body when free radicals react with fat molecules.

The body’s cells contain a lot of fat, Mochly-Rosen noted.  “It’s very easy for free radicals to find fat and oxidize it to aldehydes.”

Inside cells, the accumulating aldehydes permanently bind and damage cellular machinery and DNA.  Such damage occurs in many diseases, from heart attack and Parkinson’s to sun-induced aging of the skin.

After learning of ALDH2’s novel role in reducing the damage, the researchers searched for a molecule that could make the enzyme function even better.  They enlisted the Stanford High Throughput Bioscience Center, directed by David Solow-Cordero, PhD, to find a molecule that heightened the enzyme’s activity.

The winner of this contest was a tiny molecule that reduced heart attack damage by 60 percent in the rat model.  The molecule, Alda-1, has a surprising mode of action: it protects ALDH2 itself from aldehyde attack.  The enzyme, it turns out, was being hobbled by the very chemical it removes.

Because Alda-1 is small, it should be easy to adapt for pharmacological use, Mochly-Rosen said.  She expects the new molecule to have many possible drug applications.

“It has a huge potential use,” she said.  So far, Alda-1 has been tested only in the rat model, but Mochly-Rosen’s lab is investigating other possible applications, such as fighting neurodegenerative disease and sun damage on the skin.  The team also hopes to interest drug companies in human trials.

In addition to its lofty medical applications, Alda-1 could also have a much lowlier use: fighting hangovers.  Many nasty hangover symptoms are due to aldehyde buildup.

The tiny molecule may also improve alcohol tolerance and reduce susceptibility to free-radical diseases in people with a common ALDH2 mutation.  The mutation affects 40 percent of people of Asian descent and causes an intolerance for alcohol.

Heart disease is the leading cause of death worldwide.  However, many people with cardiovascular disease have none of the common risk factors such as smoking, obesity and high cholesterol.  Now, researchers have discovered a new link between gum disease and heart disease that may help find ways to save lives, scientists heard today (Tuesday 9 September 2008) at the Society for General Microbiology’s Autumn meeting being held this week at Trinity College, Dublin.

In recent years chronic infections have been associated with a disease that causes “furring” of the arteries, called atherosclerosis, which is the main cause of heart attacks.  Gum disease is one of the most common infections of humans and there are now over 50 studies linking gum disease with heart disease and stroke.

“A number of theories have been put forward to explain the link between oral infection and heart disease,” said Professor Greg Seymour from the University of Otago Dunedin, New Zealand.  “One of these is that certain proteins from bacteria initiate atherosclerosis and help it progress.  We wanted to see if this is the case, so we looked at the role of heat shock proteins.”

Heat shock proteins are produced by bacteria as well as animals and plants.  They are produced after cells are exposed to different kinds of stress conditions, such as inflammation, toxins, starvation and oxygen and water deprivation.  Because of this, heat shock proteins are also referred to as stress proteins.  They can work as chaperone molecules, stabilising other proteins, helping to fold them and transport them across cell membranes.  Some also bind to foreign antigens and present them to immune cells.

Because heat shock proteins are produced by humans as well as bacteria, the immune system may not be able to differentiate between those from the body and those from invading pathogens.  This can lead the immune system to launch an attack on its own proteins.  “When this happens, white blood cells can build up in the tissues of the arteries, causing atherosclerosis,” said Professor Seymour.

“We found white blood cells called T cells in the lesions of arteries in patients affected by atherosclerosis.  These T cells were able to bind to host heat shock proteins as well as those from bacteria that cause gum disease.  This suggests that the similarity between the proteins could be the link between oral infection and atherosclerosis,” said Professor Seymour.

This molecular mimicry means that when the immune system reacts to oral infection, it also attacks host proteins, causing arterial disease.  These findings could fundamentally change health policy, highlighting the importance of adult oral health to overall health and wellbeing: control of gum disease should be essential in reducing the risk of heart disease.

“This is a significant step towards a more complete understanding of heart disease and improving treatment and preventive therapies,” said Professor Seymour.  “An understanding of all the possible risk factors could help lower the risk of developing heart disease and lead to a significant change in disease burden.”

Sounding the chest with a cold stethoscope is probably one of the most commonly used diagnostics in the medical room after peering down the back of the throat while the patient says, “Aaaah”. But, research published in the inaugural issue of the International Journal of Medical Engineering and Informatics looks set to add an information-age approach to diagnosing heart problems. The technique could circumvent the problem of the failing stethoscope skills of medical graduates and reduce errors of judgment

Listening closely to the sound of the beating heart can reveal a lot about its health. Healthcare workers can identify murmurs, palpitations, and other anomalies quickly and then carry out in-depth tests as appropriate. Now, Samit Ari and Goutam Saha of the Indian Institute of Technology in Kharagpur have developed an analytical method that can automatically classify a much wider range of heart sounds than is possible even by the most skilled stethoscope-wielding physician.

Their approach is based on a mathematical analysis of the sound waves produced by the beating heart known as Empirical Mode Decomposition (EMD). This method breaks down the sounds of each heart cycle into its component parts. This allows them to isolate the sound of interest from background noise, such as the movements of the patient, internal body gurgles, and ambient sounds.

The analysis thus produces a signal based on twenty five different sound qualities and variables, which can then be fed into a computer-based classification system. The classification uses an Artificial Neural Network (ANN) and a Grow and Learn (GAL) network. These are trained with standardized sounds associated with a specific diagnosis.

The team then tested the trained networks using more than 100 different recordings of normal heart sounds, sounds from hearts with a variety of valve problems, and different background noises. They found that the EMD system performs more effectively in all cases than conventional electronic, wavelet-based, approaches to heart sound classification.

A disturbing percentage of medical graduates cannot properly diagnose heart conditions using a stethoscope, the researchers explain, and the poor sensitivity of the human ear to low frequency heart sounds makes this task even more difficult. The automatic classification of heart sounds based on Ari and Saha’s technique could remedy these failings.

Atherosclerosis is a disease of the major arterial blood vessels that is often known as hardening of the arteries; it is one of the main causes of heart attack and stroke.  An important first step in the disease is a process known as intimal thickening, whereby the intimal layer of arterial blood vessels becomes thicker because cells known as smooth muscle cells (SMCs) migrate to the area and proliferate.  The protein sLRII is thought to play a key role in this process, although its specific mechanisms of action and significance are poorly understood.  In a new study, Hideaki Bujo of the Chibe University Graduate School of Medicine, Japan, Wolfgang Schneider of the Medical University of Vienna, Austria, and their colleagues reveal that sLRII is important for SMC migration.

Levels of sLRII in the bloodstream were shown to be associated with intimal thickening in patients with poorly-regulated abnormal levels of fat in the blood.  Furthermore, intimal thickening was markedly reduced in mice lacking sLRII.  SMCs from these mice failed to migrate in response to stimulation, indicating that the reduced intimal thickening probably results from reduced SMC migration.  The authors therefore suggest that sLRII may serve as a novel marker for intimal thickening and atherosclerosis

Being male increases your risk of diseases caused by the inappropriate formation of a blood clot (a process known as thrombosis), such as heart attack and stroke, but the reasons for this are not completely understood.  However, Ethan Weiss and colleagues at the University of California, San Francisco, have used a mouse model of thrombosis to shed new light on this matter.

Thrombosis-related proteins are made in the liver, where expression of the genes containing the information needed for their generation is regulated by growth hormone (GH), which is secreted in a sex-specific manner — males secrete GH in a pulsatile fashion, whereas females secrete GH continuously.  In this study, GH-deficient mice were protected from thrombosis in the model of disease.  When female GH-deficient mice were given pulsatile GH (to mimic the manner in which GH is secreted in males) their ability to form blood clots resembled male mice.  Conversely, when male GH-deficient mice were given continuous GH (to mimic the manner in which GH is secreted in females) their ability to form blood clots resembled female mice.  The authors therefore conclude that sex-specific patterns of GH release mediate the gender-associated differences observed in susceptibility to diseases caused by inappropriate thrombosis, information that they hope will be of help in the development of sex-specific treatments for thrombosis.

New data, generated by David Ornitz and colleagues, at Washington University School of Medicine, St. Louis, have indicated a crucial role for signaling pathways that involve the protein sonic hedgehog in maintaining the blood vessels that supply the mouse heart and keep it beating.  These data have implications for drug development as they suggest that antagonists of hedgehog signaling pathways, such as those being developed as anticancer therapeutics, might have unwanted side effects.

In the study, mice lacking the ability to mediate hedgehog signaling in cells that form part of the blood vessels that supply the heart were found to die of heart failure.  This was because in the absence of hedgehog signaling the blood vessels of the heart were lost, meaning that the heart cells were no longer supplied with enough oxygen and died.  Although these data indicate a need for caution when developing clinical antagonists of hedgehog signaling, it is possible that the degree of inhibition needed to have a clinical effect on tumor development might not have the effect on blood vessels of the heart that completely eliminating expression of the protein does.

Researchers at the University of Cincinnati (UC) are looking for ways to reduce or prevent heart damage by starting where the problem often begins: in the genes.

Following a heart attack, cells die, causing lasting damage to the heart.

Keith Jones, PhD, a researcher in the department of pharmacology and cell biophysics, and colleagues are trying to reduce post-heart attack damage by studying the way cells die in the heart—a process controlled by transcription factors.

Transcription factors are proteins that bind to specific parts of DNA and are part of a system that controls the transfer of genetic information from DNA to RNA and then to protein.  Transfer of genetic information also plays a role in controlling the cycle of cells—from cell growth to cell death.

“We call it ‘gene regulatory therapy,’” says Jones.

So far, studies have identified the role for an important group of interacting transcription factors and the genes they regulate to determine whether cells in the heart survive or die after blood flow restriction occurs.

Often, scientists use virus-like mechanisms to transfer DNA and other nucleic acids inside the body.

The “virus” takes over other healthy cells by injecting them with its DNA.  The cells, then transformed, begin reproducing the virus’ DNA.  Eventually they swell and burst, sending multiple replicas of the virus out to conquer other cells and repeat the process.

Now, UC researchers are further investigating new, non-viral delivery mechanisms for this transfer of DNA.

“We can use non-viral delivery vehicles to transfer nucleic acids, including transcription factor decoys, to repress activation of specific transcription factors in the heart,” Jones says, adding that the researchers have made this successfully work within live animal models.  “This means we can block the activity of most transcription factors in the heart without having to make genetically engineered mice.”

Jones will be presenting these results at the International Society for Heart Research in Cincinnati, June 17-20.

He says this delivery mechanism involves flooding the cells with “decoys” which trick the transcription factors into binding to the decoys rather than to target genes, preventing them from activating those genes.

“We can use this technology to identify the target genes and then investigate the action of these genes in the biological process,” Jones says.

He says that this delivery has limitations and advantages.

“It can be used to block a factor at any point in time and is reversible,” he says.  “However, right now, a specific delivery route must be used to target the tissue or cell.”

Jones and other researchers are hoping that this new technology will allow them to directly address the effects of gene regulation in disease, as opposed to using classical drugs that treat symptoms or have significant adverse outcomes.

“So far, this seems to cause no adverse effects in animals,” he says.  “We are hopeful and are working toward pre-clinical studies.”

The potentially fatal heart disease LQT-2, which is characterized by the prolongation of a specific interval of time (known as the QT interval) in the heart’s electrical cycle, is caused by mutations in the HERG gene. What triggers the changes in the electrical activity in the heart (and therefore in the beating of the heart) has not been completely determined, although loud noises and emotional stress can be triggers. In a new study, a team of researchers from the Academic Medical Centre, The Netherlands, and the University of Wisconsin, Madison, has revealed that fever can also trigger life-threatening changes in the electrical activity in the heart of patients with LQT-2.

The team, led by Arthur Wilde and Craig January, measured the electrical activity in the heart over time (something that is recorded in an ECG) of two LQT-2 patients with the same HERG mutation (A558P), and found that fever was associated with prolonged QT intervals in these individuals. When this mutation was introduced into a cultured human cell line, the cells exhibited temperature-dependent characteristics, including altered electrical currents across their cell membranes at high temperatures. The authors therefore conclude that similar changes in electrical currents occur in heart cells at the high temperatures associated with fever and that fever is a potential trigger of the potentially lethal changes in the electrical activity in the heart of patients with LQT-2.

The workplace, in addition to being a place for making money, has the potential for making a dent in Americans’ struggles with obesity, according to Indiana University researchers. A study led by Whitney E. Hornsby, a graduate student in IU Bloomington’s School of Health Physical Education and Recreation, examined weight and activity levels of 56 people ages 23 to 61 who worked desk jobs. The study found that 80 percent of the employees were overweight or obese, which is higher than the general population, and the employees also reported a lower quality of life than the general population. “Obesity rates have increased while leisure time has stayed the same or increased,” said Jeanne Johnston, assistant professor in the School of HPER’s Department of Kinesiology. “We’re becoming more sedentary in our jobs. As technology improves, it makes it easier or requires us to be closer to our desks.”

• Background: The study, says Johnston, a co-author, is part of the IU researchers’ efforts to use the workplace to stimulate healthier behaviors. She said employee wellness programs typically come in two forms — they make available an on-site fitness facility that typically is rarely used, or they make available health and wellness assessments without the resources to help employees implement the recommended changes. The IU researchers are studying a behavioral change program designed to increase employees’ activity levels to the light and moderate range, rather than launching them into a full-scale workout regimen. “The transition is really important, getting to where people are in their stage of exercise and moving them along the continuum,” Johnston said. “I’m a big believer that we need to help people move from being sedentary to being active, where they can see the results. Then, they might be motivated to join a fitness facility.”