Structure Of Key Ebola Protein Discovered

Research led by Iowa State University scientists has them a step closer to finding a way to counter the Ebola virus.

A team led by Gaya Amarasinghe, an assistant professor in biochemistry, biophysics and molecular biology, has recently solved the structure from a key part of the Ebola protein known as VP35.

VP35 interferes with the natural resistance of host cells against viral infections.

"Usually when viruses infect cells, the host immune system can fight to eventually clear the virus. But with Ebola infections, the ability of the host to mount a defense against the invading virus is lost," said Amarasinghe.

This is because the VP35 protein interferes with the host's innate immune pathways that form the first line of defense against pathogens, he said.

In their research directed toward understanding host-viral interactions, Amarasinghe and his research team used a combination of X-ray crystallography and nucleic magnetic resonance spectroscopy to solve the structure using non-infectious protein samples.

A report describing the findings is published this week in the journal Proceedings of the National Academy of Sciences of the United States of America.

Now that the structure from a key part of VP35 is available, this information can be used as a template for anti-viral drug discovery.

"The next step is to use this structure to identify and design drugs that potentially bind with VP35," he said.

If a drug that inhibits VP35 function can be discovered, then the Ebola virus could potentially be neutralized.

"Without functional VP35, the Ebola virus cannot replicate so it is noninfectious," said Amarasinghe.

The Ebola virus can cause hemorrhagic fever that is usually fatal. According to the Center for Disease Control and Prevention, outbreaks have caused more than 1,000 deaths, mostly in Central Africa, since it was first recognized in 1976.

Amarasinghe co-authored this study with Daisy Leung, assistant scientist; Nathaniel Ginder, graduate student; Bruce Fulton, associate scientist; and Richard Honzatko, professor; all from Iowa State's biochemistry, biophysics and molecular biology department, together with Christopher Basler, associate professor from Mount Sinai School of Medicine in New York City and Jay Nix from the Berkeley National Laboratory in Berkeley, Calif.

Work in the Amarasinghe laboratory was funded in part by the Roy J. Carver Charitable Trust.

Vicks VapoRub may put infants at risk, study finds

The ointment is found to increase mucus production and inflammation, which can exacerbate breathing problems in children under 2, researchers say.
By Thomas H. Maugh II 

Many parents slather Vicks VapoRub on their sniffling, coughing kids when they're sick -- because, by gosh, that's what their parents did to them. For children under the age of 2, the folksy remedy could be dangerous, researchers warned today. 

Reporting in Chest, the journal of the American College of Chest Physicians, the researchers said that using the ointment to ease coughing and congestion in children of this age might lead to severe breathing problems by increasing mucus production and inflammation. 

The product's label cautions against using Vicks VapoRub on children under 2, but many parents do so anyway, putting their infants at risk, experts said.

"People don't read warnings on prescription medications, so to [read a warning for] a salve on the outside of the body that has been around for 100 years . . . I think it would be a rare parent who would do that," said lead author Dr. Bruce K. Rubin of Wake Forest University Baptist Medical Center in Winston-Salem, N.C.

Vicks VapoRub, whose active ingredients are camphor, menthol and eucalyptus oil, was first formulated in 1891 in Greensboro, N.C. National marketing began in 1905, and it gained great popularity during the Spanish flu epidemic of 1918. 

Several small studies have failed to show any medicinal benefit from the ointment, Rubin said. He suspects that the menthol in it binds to cold receptors in the throat, giving the impression that the patient is breathing more easily even when that is not the case.

The ointment's risks came to the attention of Rubin and his colleagues when they treated an otherwise healthy 18-month-old girl who was brought to the emergency room by her grandparents after her respiratory infection suddenly grew worse. Questioning revealed that the severe symptoms appeared shortly after they had put Vicks VapoRub under her nose.

The researchers were already using ferrets -- whose airway anatomy and cell lining are similar to humans -- to study infant respiratory problems. To look at the effect of Vicks, they applied the ointment directly to cultured ferret tracheal cells as well as under the noses of healthy ferrets and ferrets with tracheal inflammation similar to that of humans with a cold.

In the cultured cells, the ointment increased mucus secretion by 59%. It increased secretion by 14% in the airways of healthy animals and by 8% in those with inflamed airways. 

Because the airways of infants are much narrower than those of adults, "any increase in mucus or inflammation can narrow them more severely," Rubin said.

The ointment also slowed the action of the hair-like cilia in the throat that carry mucus away.

The team has since identified three more infants brought to emergency rooms with breathing problems after receiving Vicks VapoRub. All four recovered quickly once application of the ointment was stopped.

David Bernens, a spokesman for Vicks VapoRub manufacturer Procter & Gamble Co., said, "The safety and efficacy of the product has been determined by multiple clinical trials with over 1,000 children tested. . . . Our results are inconsistent with the claims of this study."

Bernens added that the company's post-marketing surveillance shows only three adverse incidents per 100 million units sold, with no mention of respiratory distress among them.

Conscientious pediatricians would not recommend that parents use Vicks VapoRub "because it hasn't been shown to be effective," said Dr. Daniel Craven, a pediatric pulmonologist at Rainbow Babies & Children's Hospital in Cleveland who was not involved in the study. However, he added, "we were never concerned that it would cause a problem." 

Craven argues that the new study is too small to confirm the risk from the ointment. He said he hoped "some more studies will be undertaken to further support or refute the possibility."

The report comes when pediatricians and health authorities have already been warning parents about the risks of using cough syrups and decongestants in infants and young children. 

"The bottom line is, none of them have been proven by research to work" and there are risks involved, Craven said. "There are no miracle cures for a respiratory virus infection."

The body has evolved ways to fight such infections, Rubin said -- strategies that include coughs, sneezes and mucus that traps microbes and moves them away from the throat. 

"All of those are great things," he said. "To help the body's defenses, the best things are love and hugs, warm liquids like chicken soup, and time."

thomas.maugh@latimes.com

The Rising Costs of Care And a Failing Economy Drive More Americans Into Medical Debt

By Sandra G. Boodman
Kaiser Health News


This package of stories was produced through a collaboration between The Post and Kaiser Health News. KHN is a new service of the Kaiser Family Foundation, a nonpartisan health-care policy research organization unaffiliated with Kaiser Permanente.

Pummeled by a deepening recession that is demolishing jobs and family finances, more Americans are struggling to pay their medical bills.

For years a booming economy camouflaged the burden of medical debt. Patients borrowed against their homes or whipped out credit cards, including some specially designed to pay medical or dental bills. But falling house prices and tightening credit have eliminated those options for many.

As a result, the problem of medical debt is climbing the income scale, affecting not just the poor or the uninsured. Millions of Americans covered by health insurance are paying more for less -- fewer benefits, higher co-pays and additional deductibles -- and are at risk for large out-of-pocket bills when serious illness or injury strike.

"People who are underinsured end up facing almost identical problems as the uninsured," said Karen L. Pollitz, director of the Health Policy Institute at Georgetown University. "The difference is, they paid for the privilege."

Medical debt is likely to figure prominently in the looming national debate over reforming health care.

Jim Eyler, 57, of Westminster, Md., says he needs help. The cement company manager said he spends about 33 percent of his take-home pay on unreimbursed medical bills, many connected with the advanced breast cancer his wife has been battling since 2005. "I keep wondering, where's the money going to come from?" he asked.

Experts define the underinsured as those forced to spend at least 10 percent of their income on health care, excluding premiums. But the nonprofit Center for Studying Health System Change found recently that financial pressures on families increase sharply when out-of-pocket spending on medical bills exceeds 2.5 percent of family income. New York's Commonwealth Fund has reported that 72 million adults under age 65 had problems paying medical bills or were paying off medical debt in 2007, up from 58 million in 2005. Many had insurance, and 39 percent said they had exhausted their savings paying for health care.

"There's every reason, given what's been going on, to expect the situation has gotten worse" as the economy has deteriorated, said the study's co-author, economist Sara R. Collins.

Unlike other forms of consumer debt, such as a mortgage or installment payments on a plasma TV, medical debt is typically involuntary and unplanned, the result of necessity, not desire. Consumers can't shop around for the best deal on an angioplasty or the cheapest hospital, nor in many cases can they delay treatment. Often they are forced to make decisions at their most vulnerable, because they or a loved one is sick, injured or dying.

Medical debt can quickly snowball. Consumers with unpaid bills can wind up in court defending themselves against lawsuits filed by doctors and hospitals, which typically charge the uninsured full price for care, without the hefty discounts negotiated by health plans. Debtors' wages can be garnished, liens can be placed on their homes, and their future job and housing prospects torpedoed by bad credit ratings. Those who charged medical expenses to a credit card can find that missed or late payments result in an interest rate that zooms retroactively to 29 percent.

Ironically, many people don't know that they are eligible for low-cost or free care, as Howard County officials recently discovered when they tried to register 1,100 residents in a new program, only to find that most already qualified for existing benefits but had not enrolled.

Embarrassed by unpaid bills and fearful of accruing more, many such patients postpone care until they are sicker and their illnesses are more difficult and expensive to treat.

Sheila Bell-Clifford of Alexandria has been uninsured since August, when her husband lost his job and with it their health insurance while he was being treated for metastatic cancer. She has stopped going to the doctor for treatment of her severe diabetes and skips pills, although complications landed her in the hospital two years ago. "I have to juggle them," she said of her medications, "because if I run out I'm in worse shape."

The nexus of the growing problem of medical debt and the inauguration of a sympathetic president may buoy prospects for overhauling health care, one of the top priorities of the incoming administration.

During the campaign, President-elect Barack Obama talked about his mother, who died of ovarian cancer in 1995 at 53. "In those last painful months, she was more worried about paying her medical bills than getting well," he said. Obama has said he supports creating an exemption for medical debt in stringent new bankruptcy laws.

Tackling the problem on a national level will involve replacing the mystifying welter of insurance plans with a standard, comprehensive benefits package that limits consumers' exposure to out-of-pocket costs, some experts say. Currently "there are no real standards for plans, so there are an infinite number of options," said Mark Rukavina, executive director of the Access Project, a Boston-based research and advocacy group that focuses on medical debt.

Transparency is also important, Rukavina said. Insurance policies are typically written in "intentionally confusing and unclear" language that can make it virtually impossible for consumers to figure out what is covered and how much they owe.

Economist Thomas P. Miller of the American Enterprise Institute, a conservative Washington think tank, said he believes the problem of medical debt has been exaggerated and is a symptom of the broader economic crisis. The solution, he said, should not be "to kill people with kindness" by requiring an overly expansive and expensive benefits package that could "preempt the use of resources for other purposes."

Unwilling to wait for federal action, a handful of states, most notably Massachusetts, have passed laws designed to expand health coverage or to protect medical debtors. An Illinois law passed last year caps rates that hospitals can charge the uninsured, while a New York statute bars foreclosures intended to pay off medical bills.

For now, Althea Saunders-Ranniar, a financial coach at the Bon Secours of Maryland Foundation, a nonprofit that works with low- and moderate-income residents of Baltimore, predicts that unraveling medical bills will consume an even larger part of her workday. "Everyone I see has medical debt," she said.

Many of her clients receive one bill from a hospital and five or more from physicians or labs, each of which she must parse and, possibly, negotiate. "It becomes very difficult to figure out," she said.
Comments: health@washpost.com.

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