Health and Medicine – Page 37

Shikimic Acid Shortage Sorted

Some time ago I wrote about the possibility of a shikimic acid shortage and what science is doing to address the problem. Shikimic acid, you say? The starting material for the influenza drug Tamiflu, of course!

Microbial fermentation seemed to be the way forward, but now chemists have discovered that the seeds of the sweetgum fruit – gumballs – contain significant amounts of shikimic acid. The finding means manufacturers will not have to rely on seasonal supplies of the seeds of the star anise fruit.

Thomas Poon of the W.M. Keck Science Center at The Claremont Colleges in California who heads the team says, “Our work gives the hearty sweetgum tree another purpose, one that may help to alleviate the worldwide shortage of shikimic acid.” The findings, which could help increase the global supply of the drug, Poon told the annual meeting of the American Chemical Society, this week.

Shikimic acid is used to make a generic drug called oseltamivir (Tamiflu) which is used to fight many types of flu viruses. Some health experts believe that this and similar antiviral drugs could help save lives by slowing the spread of the virus in the absence of a bird flu vaccine, which is still in development.

Bacchus Bucked

Anyone who enjoys a tipple, the fruit of the vine, a pint of hop-derived beverage, or a peaty distillate from the Scottish isles can no longer kid themselves that they were imbibing for the sake of their health. Previously, research had suggested that “moderate” drinking (of alcohol) might help prevent heart disease, but a new study published today demonstrates that this argument is intrinsically flawed.

Researchers from Australia, Canada, and the US have analyzed 54 studies that linked how much people drink with risk of premature death from all causes, including heart disease. Their findings suggest that many of the studies conducted on drinking and premature death made a consistent and serious error by including as “abstainers” people who had cut down or quit drinking due to declining health, frailty, medication use or disability. When such studies show a higher death rate for abstainers than for moderate drinkers, this result may reflect the poor health of some abstainers who recently quit drinking rather than indicating a protective effect for alcohol.

The team found only seven studies that included only long-term non-drinkers in the “abstainers” group. The results of the seven studies showed no reduction in risk of death among the moderate drinkers compared with abstainers. When the researchers combined the data from these studies, they showed that it was possible to perform new analyses that appeared to show a protective effect of moderate drinking–but only when they deliberately included the error of combining long-term abstainers with people who had cut down or quit drinking more recently.

The researchers publish the details in the May issue of Addiction Research and Theory, and concede that they have not disproved the notion that light drinking is good for health, because too few error-free studies have been performed. They suggest, however, that the extent to which these benefits actually translate into longer life may have been exaggerated.

“We know that older people who are light drinkers are usually healthier than their non-drinking peers,” explains team member Kaye Fillmore of the UCSF School of Nursing, “Our research suggests light drinking is a sign of good health, not necessarily its cause. Many people reduce their drinking as they get older for a variety of health reasons.”

So….it’s not good news for drinkers, but it’s not all bad. Let’s assume that the follow-up grant applications are already being written and in the meantime, mine’s a pint!

Magnetic Resonance Legislation

An EU directive that will become UK law by 2008, could stifle cutting edge research that uses magnetic resonance imaging (MRI) to see how medical treatments are working. The new legislation restricts the amount of time MRI operators are allowed to use the equipment each day.

Speaking at the “Science and Health” meeting this evening (March 29), Professor Penny Gowland of Nottingham University explained that, ‘The guidelines that will be imposed by the directive are overcautious and based on sparse scientific evidence. MRI is non-invasive and poses no known health risks.”

She added that the MRI community is seriously worried that the new occupational safety limits will not only curb the development of new research and medical treatments that use MRI but increase the reliance on other techniques, such as X-rays and nuclear medicine that are known hazards.

MRI produces detailed images of the body using magnetic fields and radio waves. With almost 500 MRI scanners currently being used in UK hospitals, a million examinations can be performed each year. That figure is set to increase as the government has recently invested around Â£100 million in over 100 new scanners. However, the new EU legislation could mean countless MRI-hours go to waste.

Peter Main, director of education and science at the Institute of Physics, joint organisers of the meeting, said, ‘MRI is a revolutionary, physics-based imaging technique. The Institute together with four other scientific organisations, has written to the House of Commons Science and Technology Committee to highlight our concerns over the proposed restrictions and the effects they will have both on research into and the treatment of life-threatening diseases such as cancer. We have written to Vladimir Spidla, the commissioner for social affairs at the European Commission to call upon the Commission urgently to review this directive.’

For more MRI news check out my news column on SpectroscopyNow.com

Lancet Calls for Open Access to TGN-1412 Trial Investigation

British medical journal, The Lancet, has called for an open and independent investigation of what went wrong with the small phase I clinical trial of TGN-1412 that had six men in intensive care within hours of the trial beginning.

“Commercial confidentiality should not obstruct independent scrutiny of the drug trial that led to six men becoming seriously ill in Northwick Park Hospital in London, UK,” states an Editorial in the Journal, “Both TeGenero and The Medicines and Healthcare products Regulatory Agency (MHRA) – who authorised the trial – denied The Lancet’s request to see the protocol stating that it is ‘commercially sensitive’.”

News has been terse to say the least since the initial media frenzy regarding the trial. Quite bizarrely, Northwick Park Hospital in north west London, is where eccentric UK medical comedy Green Wing is recorded.

Bird Flu Between People

Why doesn’t H5N1 pass from person to person as easily as it passes from bird to bird? After all, H5N1 can replicate very efficiently in someone’s lungs.

Japanese researchers now think they have an answer to this vexing question. The bird virus, they have found, preferentially binds to cells in different regions of the human airway from those favoured by human influenza viruses.

Flu viruses infecting humans and birds are known to home in on slightly different versions of the same molecule, found on the surface of cells that line the respiratory tract. Yoshihiro Kawaoka and colleagues report in today’s Nature the effect this has on patients. Whereas the version of the molecule preferentially bound by human viruses is more prevalent on cells higher up in the airway, the molecule that is preferentially targeted by avian viruses tends to be found on cells deep within the lungs, in the air sacs, or alveoli, of the lung.

This may explain why human-to-human transmission of H5N1 remains uncommon, explain the authors. The virus may preferentially enter cells deep down inside the lungs, meaning that an infected person is less likely to spread the virus by coughing or sneezing. The researchers add, however, that should the virus ever acquire the ability to infect cells higher up in the airway then it may make the leap to a human to human infectious disease.

Parallel findings are also published today in Science, by Thijs Kuiken and colleagues. They have identified alveoli type II pneumocytes, scavenging cells within the lumen of the alveoli as the cells to which H5N1 predominantly attaches. These findings are in contrast to the received wisdom that avian influenza viruses have little or no affinity for cells of the human respiratory tract.

Stretching a Point

A press release from the Journal of Investigative Dermatology describes the latest research into stretch marks. The release says stretch marks are “unsightly” and describes them as a “disorder”. Fair enough. It then goes on to discuss the finding that women with this disorder, appear to be at increased risk of pelvic prolapse. How could this be and what are the warning signs?

Like stretch marks, pelvic prolapse is a connective tissue disorder and pelvic weakness is a serious condition caused by deterioration of support structures that can result in pressure, pain, vaginal bulge and/or urinary incontinence. The scientists who report their results explain that pelvic prolapse is an extremely under-reported condition with no official data as to how many women suffer from the condition. Tracked cases in the US, however, show more than 300,000 procedures are performed annually to repair the condition, which has been previously associated with pregnancy. This new study, however, found that stretch marks were twice as common in women with prolapse as those without, hinting at a hitherto hidden connection.

Stretch marks occur when skin is stretched beyond its usual capabilities and normal production of collagen is disrupted. As a result, scars or stretch marks form. Alexa Kimball and colleagues reviewed results from a survey issued to urogynecology and dermatology patients. Participants ranged in age from 25-90 with an average weight of 152 pounds (70 kg).

Analysis of multiple variables identified stretch marks as the only significant predictor of pelvic
prolapse. Follow-up studies will further investigate the incidence and correlation of these two connective tissue disorders and how genetic factors contribute to incidence. Research will also include prospective studies to validate findings and identify predictive markers to prevent the progression of this condition.

The paper is available through www.jidonline.org

Double your Money in Bird Flu Lottery

It’s like buying two tickets instead of one for the national lottery, you may shorten the odds ever so slightly, but there’s still very little chance of winning. That should be your first thought on hearing that the strain of avian influenza currently making the media sweat has evolved into two distinct variants. That’s the big news emerging from the International Conference on Emerging Infectious Diseases in Atlanta this week.

Rebecca Garten of the US Centers for Disease Control and Prevention reports that she and her colleagues analysed more than 300 H5N1 samples from infected birds and people between 2003 and summer 2005, and found two distinct sub-types of the virus. The genetically distinct H5N1 strain is thought to have emerged in 2005 and infected people in Indonesia.

The concern is that the existence of this variant points to an increased risk of a human-transmissable form of avian influenza emerging at some stage. Of course, the emergence of distinct strains of a single type of flu virus is nothing remarkable. Flu viruses are notoriously quick to evolve. After all, they wouldn’t be endemic in their host populations if they weren’t, as a second wave of infection would simply be defeated by the already primed immune defences. Evolution provides each successive strain with a new set of proteins to avoid detection by the immune system. Regardless, H5N1 is still a bird virus, it only very rarely infects people. It will take more than a simple single mutation to allow it to leap from a bird host environment to humans and even then, many researchers concede that it is likely to lose virulence when it does so.

Antiperspirants Cause a Stink

Philippa Darbre of the University of Reading, England, has published a review of the putative health effects of organometallic compounds that mimic estrogen and could increase the burden of “aberrant oestrogen signalling within the human breast”. Of particular relevance to public health is her suggestion that the aluminum compounds used in the manufacture of underarm antiperspirants may somehow be involved in an increased risk of breast cancer. The paper is already causing a stir in the UK, however, it is also causing controversy particularly because it does not represent any new experimental evidence but draws new conclusions from other studies.

You can read the full story in Issue 53 of chemistry webzine Reactive Reports, out now!!!

Nothing to be Scared of

SciScoop contributor and University of Buffalo medic Bradford Frank sent us a copy of his latest book “Terror Unleashed” recently. Frank’s hypothesis is that the human race is soon to face a whole range of major crises from bird flu and oil shortages to financial collapse and devasting terrorist attacks. He begins by emphasising that the ideas he presents, are just that, ideas, and that there is no proof any of the events he describes will come to pass. However, what he does hope to achieve is to raise awareness of the potential threats to you, your family, your nation, and your planet.

You can read it, go into denial, and dismiss it as pure, unadulterated scaremongering. Or, you can absorb the warnings, make provision for their occurrence, and feel smug and fairly secure should they ever come to pass. For instance, it does seem like it is only a matter of time before we enter a period of financial depression, after all the boom-bust cycles of modern economics are well founded in history. Again, bird flu is the virus of the day, but it needn’t be H5N1 that leads to an influenza epidemic on a bigger scale than that of 1918-1919, there are dozens of emerging viruses just waiting to spring across the species gap from their current animal hosts. As to the impending oil shortage, global warming, nuclear terrorism, and electromagnetic pulses…we’ll certainly know about them if and when they hit.

Frank’s book is scaremongering. That’s for sure. And, if he weren’t a well-respected MD at a well-known US university, he might be the kind of man to walk the city streets with a placard proclaiming “The End of the World is Nigh”. The only trouble is, he might actually be right.

Frank’s website points to resources that could help in an emergency, but I also suggest you check out Stephen Jones’ Bird Flu Survival Guide.

Critical Trials TGN1412

The BBC reports today that six men are on the critical list after becoming seriously ill while taking part in a clinical trial of a new drug for treating leukemia and arthritis: BBC Report.

The previously healthy young men were being paid (up to Â£150, $330 a day) to take part in the early stages of a trial of the novel drug TGN1412. However, within hours of their first injection, they reacted adversely (suffering multiple organ failure) and were put in intensive care. The two men receiving placebo in the trial are fine.

The compound in question is biopharmaceutical company TeGenero’s humanized CD28-SuperMAB (TGN1412) which is in trials for rheumatoid arthritis and B-CLL (B-cell chronic lymphocytic leukemia). Following standard toxicity studies it was entered into initial clinical trials. “The drug was developed in accordance with all regulatory and clinical guidelines and standards,” explained Dr Thomas Hanke, Chief Scientific Officer of TeGenero AG, in a statement, “In pre-clinical studies, TGN1412 has been shown to be safe and the reactions which occurred in these volunteers were completely unexpected.”

Adverse reactions to drugs in clinical trials are exceedingly rare, but then TGN1412 is not your everyday small molecule type drug. TeGenero developed this drug, a superagonistic monoclonal antibody, with the aim of balancing T cell (a type of white blood cell) activation by triggering receptors on another group of white blood cells known as T lymphocytes. Today’s events are likely to provide animal rights activists with new fodder to push for animal testing to be banned, they will undoubtedly cite this unforeseen problem as further evidence that animal tests cannot show how a drug might act in people.

Ganesh Suntharalingam of Northwick Park Hospital told the BBC that, “The drug, which is untested and therefore unused by doctors, has caused an inflammatory response which affects some organs of the body.” Why this should be so is unclear. The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has withdrawn authorisation for the trial (obviously) and doctors in other countries have been sent a warning not test it.

Sciencebase will keep you posted on events as we hear them, in particular we’ll try to bring you the results of the ongoing investigation as soon as we can. It may emerge that a clinical error is to blame rather than there being a biological problem with the drug itself, we will have to wait and see.

This very unfortunate incident comes just one day after widely acclaimed findings were revealed showing how the totally unrelated statins could reverse atherosclerosis. Such positive results that inspire public confidence in the pharmaceutical industry are almost as rare as the present negative result!

Richard Ley of the Association of the British Pharmaceutical Industry was reported as saying “This is an absolutely exceptional occurrence.” and “cannot remember anything comparable.”