Monthly Archives: October 2010

I got (circadian) rhythm

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grandfatherclock.jpgThis weekend, clocks in the UK will ‘fall back’ one hour; a week later, the US will follow. This sudden change might leave you feeling slightly discombobulated, but chances are, your internal clock will soon adjust to compensate. Some people aren’t so lucky; perturbations of circadian rhythm are thought to be a factor in sleep disorders and some psychiatric conditions like bipolar disorder, according to a study published last month in PLoS One.

The master timekeeper of the body is in the suprachiasmatic nuclei (SCN), a tiny pair of neuron clusters located in the hypothalamus. But there are also peripheral body clocks, located in organs like the liver, and even within individual cells. Synchronizing these clocks means taking non-environmental cues, like feeding patterns, into account.

A recent paper in Cell described how an enzyme called poly (ADP-ribose) polymerase 1 (PARP1) coordinates the master clock of the SCN with circadian rhythmic gene expression in the liver. Mice deficient in PARP1 were slower to respond when their feeding regimen changed. The authors also found that PARP1 interacts with two key circadian rhythm regulators, CLOCK and BMAL-1. These transcription factors were also recently found to be involved in muscle maintenance by targeting MyoD, a master regulating protein of myogenesis.

Though researchers have been able to peer into the circadian clocks of model organisms like mice and fruit flies, it was unclear whether or not the nematode Caenorhabditis elegans had a circadian rhythm at all. A genome-wide analysis in PLoS Biology found the first evidence of gene expression patterns in C. elegans influenced by circadian rhythm. The authors found that temperature and light influenced the expression of up to 9% and 4% of all the genes in the organism.

Enjoy the extra hour of sleep!

Image by stevendepolo via Flickr Creative Commons

TEDMED 2010: Reach out and touch science… Martha Stewart did

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As you may have figured from our Twitter feed (https://twitter.com/naturemedicine), Nature Medicine has spent the past couple days camped out at the TEDMED meeting in San Diego, California. The annual medical technology conference kicked off on a strong note, when singer Charity Tillemann-Dick serenaded the audience with opera. The performance was moving, but what really left the audience breathless was the fact that she had undergone a double lung transplant a little over a year ago.

Tillemann-Dick’s story set the theme for much of the conference: the pervasive message was that technology can empower patients, but that to really live patients have to actively engage with their treatment. (In Tillemann-Dick’s case ‘really living’ means singing, and ‘engagement’ involved retraining her new set of lungs.)

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Efforts gel to fast-track anti-HIV drug

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In July, reports of a successful anti-HIV vaginal gel wowed the the International AIDS Conference in Vienna. Now the US Food and Drug Administration is looking to speed the gel’s approval, according to the drug’s makers, who met with the agency last week.

Henry Gabelnick, the executive director of CONRAD, one of the groups developing the tenofovir gel, told Reuters that the gel has been fast-tracked, meaning that data can be submitted as it becomes available.

Results from the first study, involving 889 South African women, showed that the group of women using the gel had an infection rate 39% lower than the placebo group. And among women who used the gel most consistently, the rate of infection was lowered by 54%. But the FDA will want to see results from the VOICE trial, expected to conclude in 2013 or 2014, before seriously considering the gel for approval.

Breast isn’t always best

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breastpump.jpgYesterday, the New York Times reported that while items like acne creams and denture adhesive are eligible for tax breaks under the new US health care law, breast pumps are not. Breast-feeding boosters like La Leche League are, naturally, up in arms, but the US Internal Revenue Service says that the pumps do not fall under the umbrella of preventative medicine, since breast milk is primarily nutrition.

To counter the IRS, breast-feeding advocates point to research showing that breast-feeding transfers essential antibodies from mother to child. There’s also research suggesting that bacteria in mother’s milk plays a key role in building up a healthy community of intestinal microflora.

But in certain circumstances, breast-feeding can be a vector for harmful microbes as well. In February, the US Centers for Disease Control (CDC) reported the case of a mother in Brazil who, after she received a yellow fever vaccine, passed the virus to her infant through her milk. Hepatitis B virus (HBV) has been detected in the milk of HBV-positive mothers, though it’s unclear if the virus can actually be transmitted through breast-feeding; the most common method of mother-to-child HBV transmission is during delivery itself. If a Hepatitis C-positive mother has cracked or bleeding nipples, she runs a higher risk of transmitting the virus to her infant. UNICEF estimates that if an HIV-positive mother breast-feeds, she’ll pass the virus to her child 5 – 20% of the time.

It’s worth noting that another US government agency, the Transportation Security Administration, classifies breast milk as ‘liquid medication’, which is why mothers are allowed to bring more than three ounces of it on a plane.

Image by planet _oleary via Flickr Creative Commons

NICE guys finish last in 2013

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In three years time the National Institute for Clinical Health and Excellence (NICE) will be taking more of a back-seat role in the UK drug approval process. At the Royal Society of Medicine in London yesterday, the British health minister Earl Howe said that NICE will take on a more generalized advisory role, instead of conducting cost-effective analyses for individual drugs, according to the In Vivo blog. When those changes kick in, the National Health Service (NHS) will also have the option of ignoring the agency’s advice as to which drugs it can afford to buy.

Why 2013? That’s when the UK’s current drug-pricing arrangement with pharmaceutical companies, the Pharmaceutical Price Regulation Scheme (PPRS) is set to expire. The PPRS is based on capping drug companies’ profits, rather than the prices of the drugs themselves. In place of that agreement, Howe said the government will introduce a new ‘value-based pricing’ system focusing on adjusting the price of individual drugs. How this pricing will be decided is still unclear. Many governments in Europe have already slashed drug prices by as much as 25% to make their health budgets stretch a little further.

Although half of the 18 agencies within the Department of Health are being considered for elimination or reorganization under the Conservative government’s cost-cutting measures, NICE was spared the government axe. But all the while, there have been signals that NICE would soon be put on the back burner. In June, after NICE gave the thumbs-down to Tyverb, an oral breast cancer drug, the Department of Health said in a statement that NICE “must be allowed to continue to issue guidance free from political interference. However, we believe that there are fundamental failings within the wider system for drug pricing and access”.

NICE has also come under scrutiny from academics for the way that it determines cost-effectiveness. In 2009, for instance, a paper in PLoS Medicine determined that randomized clinical trials, which NICE heavily relies upon when advising the NHS, often fail to indicate how a drug actually performs in clinical practice.

If the agency hopes to stay relevant in the years ahead, it looks like it’s time to play nice.

I like… my breast cancer activism with substance

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pinkribbonThis time of year, the leaves are turning red and yellow and orange, but just about everything else is blushing pink. That’s right: it’s Breast Cancer Awareness Month! The Susan G. Komen for the Cure Foundation has raised more than $1.5 billion for breast cancer research since it started in 1982, and $55 million a year comes from corporate marketing partnerships (including the special edition KFC bucket). We’ve covered these questionable ‘pinkwashing’ practices before. And this October, there’s a new wrinkle to breast cancer activism: half-hearted online awareness campaigns.

The iconic pink ribbon debuted in the early 1990s, and was popularized after the Komen Foundation handed ribbons out to participants in the 1991 Race For the Cure in New York City. Corporations soon discovered that affixing the symbol on their product not only helped their image, but their profit margin as well. In 2006, Campbell’s Soup saw its sales double when it offered pink versions of its iconic cans. In exchange, the company donated $250,000, or a mere 3.5 cents per pink can, to the Susan G. Komen Foundation. When it comes to buying pink products, it’s important to read the fine print: a company may have a cap on the amount of money it’ll donate, and some do not specify what organization the donations are going towards.

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The ‘bitter’ truth about lungs: they can taste

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Lungs_diagram_simple.jpg

The same bitter taste receptors that are found on the human tongue also exist in the smooth muscles of the lungs, according to research published online yesterday in Nature Medicine. The unexpected findings could lead to improved treatments for asthma, emphysema and chronic bronchitis.

Stephen Liggett and his colleagues at the University of Maryland School of Medicine in Baltimore stumbled upon the taste receptors when looking for G protein-coupled receptor proteins in airway smooth muscle cells. The discovery intrigued them because taste receptors, when activated, typically increase the amount of calcium within the cell, causing muscle constriction. So Liggett’s team assumed that this chemical flux would constrict the lung tissue.

But when they stimulated the receptors in a mouse model of asthma with compounds known to activate bitter taste buds, including quinine and saccharine, the researchers were surprised to find that the muscles relaxed, presumably because the receptors in the lungs evolved to help people breathe more easily in the presence of bitter foreign substances, such as those secreted by pathogenic bacteria during bronchitis or pneumonia.

Liggett’s team is now actively screening compounds to find the ones that most effectively and safely open lung airways.

“There have not been any new direct bronchodilators in the drug discovery pipeline in over five decades,” Liggett told Nature Medicine. “And we have now found a pathway and multiple drugs that activate that pathway that provide direct bronchodilitation that’s more extensive than any known pathway or compound to date.”

The work will appear in the November issue of the journal, and an extended interview with Liggett can be heard on next month’s podcast.

Image: Wikimedia

In season, atmospheric conditions can drive disease

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seasonleafsnow.jpgWhen winter comes, it usually brings more than just snow. The frigid temperatures coincide with a predictable uptick in colds and influenza. Lately, though, researchers are finding some seasonal patterns in conditions one wouldn’t necessarily expect to be tied to the calendar.

In August, scientists reported new insights into the seasonable variability of multiple sclerosis. They had examined 939 brain scans taken from 44 individuals with multiple sclerosis over a period of three years. The scans used magnetic resonance imaging to measure edema as an indicator of new lesions in the brain. As they reported in Neurology, the researchers discovered that between March and August, the subjects suffered brain lesions at a rate that was, on average, two to three times higher than during the rest of the year. (Click here to continue reading)

Image by Dawn via Flickr Creative Commons

Disaster in the time of cholera

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haitisupplies.jpgHaiti is back in the news this morning, as its Ministry of Health just announced that lab tests have confirmed that cholera is responsible for an outbreak of diarrhea in rural areas. The epidemic has sickened more than 1,500 and killed at least 150, according to the World Health Organization (WHO). For months, aid organizations have been warning that crowded conditions amongst refugees from January’s devastating earthquake could lead to rapidly spreading illnesses.

“This is the first major epidemic that has taken place since the earthquake as far as I’m aware,” Andrew Marx, spokesman for medical aid group Partners in Health, told the Wall Street Journal.

Access to clean water is of paramount importance to disaster victims, as many aid groups well know. Recent floods in Pakistan have been accompanied by fears of cholera outbreaks; in August, the WHO reported that more than 18,000 people were treated for acute diarrhea in flood-affected areas. After the 2004 Boxing Day tsunami in southeastern Asia, officials feared that cholera could double the more than 230,000-person death toll, but major outbreaks failed to materialize.

Image by the US Navy via Wikimedia Commons

Call for renewed focus on rare mutations grows more common

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By Melinda Wenner Moyer

In the past five years, scientists have identified more than 3,000 common genetic mutations associated with diseases including cancer, Alzheimer’s and diabetes, thanks to insights gleaned from genome-wide association studies (GWASs). But the inherent value of these studies has come under scrutiny, in part because they largely ignore rare mutations. Given this flaw, researchers have called for renewed focus on the rare mutations that might be more likely than common ones to cause illness.

The GWAS approach involves comparing the genomes of healthy people with those suffering from illness to pinpoint disease-associated single nucleotide polymorphisms (SNPs) typically present in at least 5% of the population. “A GWAS study is meant to capture most of the common variation in the genome, and that’s something it does very well,” says Jonathan Sebat, a geneticist at the University of California–San Diego. (Click here to continue reading)