Spectroscopy – Page 5 – David Bradley

Asian flush, blush, glow

UPDATE: March 9, 2010 – Baclofen, the muscle relaxant and GABA agonist is being touted once more as a treatment for alcoholism. Read my thoughts on sibling science site SciScoop.com.

As with much of medical science, the appearance of a fascinating research paper and an accompanying press release do not usually mean that a new pharmaceutical intervention, a medicine, is ready to be prescribed to patients on the very day that the paper appears. The drug discovery, research, and testing processes are much more long-winded than that.

One example was a recent paper on Alda-1, the simplified name for N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide, a small organic molecule that activates the enzyme ALDH2 (aldehyde dehydrogenase 2). ALDH2 is involved in metabolising the aldehyde byproducts of other substances in the body particularly alcohol.

In September 2008, Alda-1 was touted by the media as a “new drug hope for controlling heart damage”. By activating ALDH2 it was suggested that those people who have an inactive form of that enzyme (some 40% of East Asians and people of East Asian descent) could be treated with the compound to preclude the cardiotoxicity of aldehydes formed when they drink alcohol.

More recently, the same researchers involved in the 2008 study, Thomas Hurley of the University School of Medicine in Indianapolis and Daria Mochly-Rosen, of Stanford University School of Medicine, and colleagues, have published a crystallographic study showing more details of how Alda-1 works to activate ALDH2. You can read my write-up on this work today in the latest issue of the X-ray ezine on SpectroscopyNOW.com.

However, press releases are notoriously hopeful about the actual use to which a piece of biomedical research might be put so I asked Hurley for some additional insight into the likely fortunes of Alda-1.

“Alda-1 is not ready for human trials, nor is it ever likely to be,” he told me. “Its potency is relatively low for an effective in vivo agent, especially when one accounts for its solubility.”

The compound is, as those in pharma research will have realised from the off, simply a lead compound. A compound that researchers will use as the starting point for novel and potentially more efficacious and more soluble compounds, analogues, that would be designed for testing and clinical trials.

“We have much work to do on this before clinical trials can even start to evaluate whether this is an effective strategy in vivo,” conceded Hurley, “I doubt there will anything ready for clinical application for 7-10 years, unless we get really lucky here in the next year with our analogue design and testing,” he adds.

One thing that the original media attention did get right is that Alda-1 might eventually lead to a primary clinical application in the area of cardioprotective effects. This would be rather than it being developed as a drug to allow East Asian drinkers with the ALDH2 mutation to imbibe more alcohol than their flush response, nausea, and palpitations would normally allow them.

“Its use as an activator for alcohol metabolism will, hopefully, be regulated,” Hurley told me, “There are broad ethical issues associated with an application toward reducing alcohol intolerance in the East Asian population or individuals of East Asian descent.”

He points out that pescribing a drug descended from Alda-1 to activate mutant ALDH2 would be like curing a lifestyle issue (alcohol intolerance) and replacing it with an increased risk for a devastating disease – alcoholism. “Currently, there is relatively low risk of alcohol abuse or alcoholism in those individuals who are intolerant to ethanol consumption, so ‘curing’ the intolerance is very likely to lead to an increase in the prevalence of these devastating diseases in these low risk populations,” Hurley added.

Once a drug is developed for the cardioprotective benefits emerges on to the market, however, you can bet your last Yen that a blackmarket will quickly emerge where there are large populations of East Asians, for a pill that would allow otherwise lightweight drinkers to put themselves under the table without the flushing, nausea and palpitations. Of course, it won’t ever preclude the need to consider the health risks of excessive drinking and to seek alcohol treatment if one’s drinking becomes a serious problem.

Perez-Miller, S., Younus, H., Vanam, R., Chen, C., Mochly-Rosen, D., & Hurley, T. (2010). Alda-1 is an agonist and chemical chaperone for the common human aldehyde dehydrogenase 2 variant Nature Structural & Molecular Biology DOI: 10.1038/nsmb.1737

Latest science headlines

Time to bring you up to date on the latest science headlines I’ve put together for other sites this last couple of weeks, so here’s a quick round-up:

On the SpectroscopyNOW site, this issue, I covered natural chemicals that can help sunflowers soak up toxic cadmium from the soil (another example of the phytoremediation process I discussed in more detail on Sciencebase.com recently). I also describe a new approach to spectroscopy that could help chemists work out the absolute structure of natural products with medicinal potential.

In the same issue, under the X-ray banner, I explain how US researchers have for the first time homed in on the role of the trace element selenium in male infertility. Their work offers some new clues as to what leads to malformed sperm in some cases.

I also report on yet another “omics”, in which conservators take a leaf out of the biologists’ handbook to find a way to judge a book not by its cover, but by its odour.

Over, on the Intute physical sciences blog, formerly my monthly Spotlight column, I reported on proton spin, magnetic wind, and the latest catalysis research with implications for industry.

And, ever present, the ubiquitous and omnipresent Alchemist. First to fall under The Alchemist’s crystalline gaze is Korean work into coating yeast particles with a protective silica shell to stabilize the organism for new lines of research. Geochemistry billions of years old reveals a sulfidic past and answers questions about how the Earth got its oxygen-rich atmosphere. In biophysical chemistry, US scientists have found a way to extend the redox range of copper-containing proteins and in computational chemistry Dutch scientists explain precisely how hydrogen interacts with copper surfaces. Good news for those fearful of mercury dental fillings, as a new composite material emerges from polymer and nanochemistry research. Finally, a cash injection from US recovery funds could see the establishment of yet another “Facebook for scientists”, only this time it’s aimed squarely at American institutions.

Sniffer, E coli Clues, Graphene

The second batch of physical science and biomedical research news in the SpectroscopyNOW ezines are live:

Optical sniffer detects poison gas – US researchers have developed an optoelectronic nose that can sniff out toxic gases. The sensor is fast and inexpensive and could be used to detect high exposure risk to hazardous industrial chemicals.

E coli clues – New clues as to the virulence of the potentially lethal bacterium Escherichia coli O157:H7 has emerged from structural and functional relationship studies of its autotransport and proteolytic EspP proteins. A comparison with X-ray diffraction results reveals important clues about these proteins.

Imaging a semiconductor sandwich – A technological mash-up between graphene and the semiconductor gallium arsenide as characterised by optical microscopy and Raman spectroscopy and other techniques could pave the way to hybrid electronics devices that bridge the gap between current silicon circuitry and future molecular electronics

Dental Lead, Lung Cancer and Monopoles

This week’s ezines on SpectroscopyNOW are now live, featuring a breath test for lung cancer, magnetic monopoles, a way to boost fuel cells, and reducing toxic waste from dental surgeries.

Extracting the dental lead – Lead contamination in the black paper used to mask dental X-ray paper has been determined for the first time using AAS. The worrying results suggest that the used material represents an environmental waste problem requiring pre-treatment before disposal.

I asked the researchers to outline the importance of their study. Team leader Debora Guedes told me that, “There are still more than 600 million packets of intraoral film exposed each year in the USA alone, and much more elsewhere in the world. The volume of potential waste materials is significant,” she says.

She pointed out that while attention has previously been given to the disposal of the lead foil used against backscatter radiation that can fog an X-ray image and also to avoiding lead-lined boxes to store intraoral dental X-ray film, lead contamination of the black paper used to help exclude light from the film, or the paper or plastic wrapping of the film and lead foil has been ignored entirely, she adds. “This study is an important public health contribution as it indicates that this neglect is of potential importance,” Guedes told me.

A breather for lung cancer suspects – Researchers in Israel have used cheminformatics methods to “train” an array of gold-nanoparticle sensors to rapidly distinguish between the out breath of lung cancer patients and that of healthy individuals.

Monopoles apart – Four research papers, two of which were published in the journal Science, this week, and two submitted to the physics preprint archive, suggest that a long-sought icon of fundamental physics has finally been discovered – the magnetic monopole. This fundamental research could have enormous potential in materials research, nanotechnology, and eventually instrumentation.

Fuelling nanotube potential – X-ray diffraction and X-ray photoelectron spectroscopy have been used to analyse semimetallic titanium dioxide nanotubes with potential in fuel cell technology.

Stinging Heavy Metal Resistance

Head-banging science news with a spectroscopic bent from my latest posts on the SpectroscopyNOW ezines, live June 15.

A medical tale in the sting – The venom of the eusocial bee contains three novel antimicrobial compounds known as lasioglossins, which have been structurally characterised by NMR spectroscopy. The compounds offer a new avenue for developing new antibiotics that might defeat drug-resistant bacteria.

Marine surfactant soaks up heavy metal – Atomic absorption spectroscopy (AAS) and other techniques have been used to demonstrate the effectiveness of a natural surfactant molecule in removing heavy metals from solutions for potential bioremediation applications.

Topical resistance – Crystallography by UK scientists may have uncovered the mechanism by which quinolone drugs interact with DNA and bacterial topoisomerase and so point to a better understanding of how resistance to this class of drugs emerges in meningitis and pneumonia.

Exhausted grapes fit only for compost – Multivariate analysis of the physicochemical, chemical and biological parameters of winery and distillery composts could point the way to improving the use of these generally intractable waste materials.

Cannabis Cancer, Toxic Waste, Antibiotics

The latest science news with an analytical bent from yours truly, now available in the SpectroscopyNOW ezines:

Cannabis blow back – A highly sensitive new chemical test has allowed European scientists to obtain “convincing evidence” that marijuana smoke damages DNA in ways that could increase the risk of cancer.

Toxic shock – Researchers in Spain are evaluating the “ecotoxic” properties of hazardous and toxic wastes for the aquatic environment. They suggest that the ecotoxic profile of a given waste stream can be derived from a novel battery of bioassays using statistical techniques that reveal whether dangerous levels of compounds toxic to frogs and fish are present and whether or not uber-toxins* like dioxins are at unsafe levels.

Chemical directors – Chemistry often all about activation. Now, UK chemists have found a way to control and direct the activation of important molecules used to synthesise pharmaceutical and agrochemical products. Their work also provides new insights into how bond activation works.

Enzymic activity – Researchers have obtained the first three-dimensional crystal structure of an enzyme that contains iron and helps soil microbes fend off invaders and rivals. The enzyme hydroxyethylphosphonate dioxygenase (HEPD) used by the Streptomyces soil microbe could lead to new agricultural technology, chemical catalysts, and perhaps even novel antibiotics that defeat bacterial resistance to conventional drugs.

*Yes, I know the word toxin applied only to compounds naturally derived and that attaching the uber mock prefix to this word is probably also misplaced as dioxins have a much worse reputation than they deserve, but I couldn’t help myself and they are very poisonous.

Red Hot Spectral Alchemist

spectral-alchemist This week, The Alchemist learns of encapsulated capsules that could emulate cells, a new glassy material for preventing debilitating leaks in solid oxide fuel cells, and a computer model that might help us develop a vaccine for H1N1 type A influenza. Also, under his gaze are ionic liquids developed to dissolve wood and the cancer drug that worryingly wipes away travelers’ fingerprints. Finally, a reminder that the RSC has drawn structure database Chemspider into its web.

Over on SpectroscopyNOW, I’ve got three more news topics on cancer, Alzheimer’s disease, and mushroom poisoning:

Cancer-killing CNTs – Carbon nanotubes have allowed spectroscopists to track the movement of cancer cells through the blood and lymph systems. They also act as markers for subsequent laser therapy to kill the cells, pointing the way to an entirely novel diagnostic and treatment regime for cancer, and potentially metastasised cancer.

Early ID of AD – New software for the automated analysis of MRI brain scans could help specialists identify cases of mild cognitive impairment years before full-blown Alzheimer’s disease is apparent, according to US researchers.

Toxic fungal triangle – Chemical analysis has revealed the lethal toxic culprit in a spate of recent food poisoning incidents among Japanese people eating mushrooms including the species Russula subnigricans. The compound, essentially a ring of three carbon atoms with an acid group, cycloprop-2-ene carboxylic acid, is well known to synthetic organic chemists and offers new insights into a potentially lethal condition known as rhabdomyolysis. The researchers tell me that aside from helping us understand this curious condition the compound probably has no biological use, it failed anticancer and antibiotic tests, they told me.

Oh, the red hot allusion..? Well, at the time of writing, I’m working wirelessly in my back garden under a sun shade in sweltering English heat…it’s almost the weekend and we have high expectations of early-summer storms drowning our Saturday barbecue party…ever the pessimist, eh?

Curious X-shooter Antibiotics

A sneak preview of my spectroscopyNOW ezine headlines for June 1:

Bi-curious microcylinders – A team in the US has produced micrometre-wide discs and elongated rods from bi-coloured and multicoloured compartments. The composite materials could have novel applications in diagnostics, drug delivery, and a new type of display technology.

X-shooter snap the cosmos – The European Southern Observatory’s Very Large Telescope now has an X-shooter, a second-generation spectroscopic instrument that can record the entire spectrum of a celestial object in a single shot – from the ultraviolet to the near-infrared – with high sensitivity. This unique new instrument will be particularly useful for the study of distant exploding objects known as gamma-ray bursts.

Attacking antibiotics – The crystal structure of a penicillin-binding protein 1B (PBP1b) has been obtained by a team in Taiwan. The research could represent a major step forward in the development of novel antibiotics against resistant strains of bacteria.

Light, Trials, Balls

hollow-ball In my SpecNOW science news column this week:

C60, C80, C0, Go! – X-ray crystallography, nuclear magnetic resonance spectroscopy, and other techniques have allowed German chemists to demonstrate their synthesis of the first non-carbon analogue of the C80 fullerene molecule. And yes, the title is an allusion to the Malcolm McClaren fashion vehicle of the post-punk era, Bow Wow Wow.

Photosynthetic disorder – An international team has used solid state NMR spectroscopy to determine the structure of the chlorophyll molecules in green bacteria that are responsible for harvesting light energy. The discovery might ultimately lead to artificial photosynthetic systems.

Clinical reflections – Clinical research studies into drug efficacy and side effects have often been laborious and time consuming, new software that analyses “anonymised” patient electronic medical records could reduce investigation times from months to minutes.

This week, The Alchemist observes evolution in the test tube in this week’s issue and ponders the notion of a plastic pancreas. The vomeronasal organ of mice reveals new chemical secrets about rotten food and sickly individuals while high-power lasers go down the tubes. Microscopic molecular balls also caught the Alchemists eye while kudos goes to soft matter pioneer George Whitesides for his winning the inaugural Dreyfus Prize in the Chemical Sciences.

Heavy Metal Packaging

Researchers in Argentina have developed a new approach to testing food packaging for trace amounts of the toxic heavy metal cadmium.

Cadmium is one of several additives used extensively in the manufacture of plastics. Regulations limit the concentration of cadmium allowable, of course. In the European Union that limit is 100 milligrams per kilogram. But, the toxic metal has a long biological half-life (10 to 30 years) and so essentially accumulates in your body on repeated exposure.

Analytical advances aside, I asked Rodolfo Wuilloud of LISAMEN, how big a problem is cadmium in food packaging? Should the public be concerned?

“The presence of heavy metals in plastic food packaging is an important problem considering the extended use of this type of packaging,” he told me, “Concentration of heavy metals should be limited in order to reduce their potential health impact resulting from their possible migration from the packaging material into food and also to ensure that such substances are not released into the environment, for example in emissions or ash when packaging is incinerated, or in leachate when packaging is landfilled.”

He adds, that it is important that the public should be aware of this problem. Concern is the first step towards getting governments to change environmental policies. “It is necessary to introduce national measures to ensure that packaging is allowed on the market only if it complies with certain requirements in their composition so as to prevent the addition of noxious heavy metals to packaging and to reduce the impacts on the environment and human health,” Wuilloud’s colleague Estefania Martinis says.

The team used room temperature ionic liquids (RTILs) as an online pre-concentration medium for flame atomic absorption spectrometry analysis of trace cadmium in plastic food packaging materials. Critically, the use of non-volatile, non-flammable RTILs instead of volatile and flammable organic solvents is helping in this regard by allowing analytical scientists to breathe new life into powerful techniques, such as atomic absorption spectroscopy, that have been labelled “old fashioned” in recent years as other methods emerged.

Martinis, E., Olsina, R., Altamirano, J., & Wuilloud, R. (2009). On-line ionic liquid-based preconcentration system coupled to flame atomic absorption spectrometry for trace cadmium determination in plastic food packaging materials Talanta, 78 (3), 857-862 DOI: 10.1016/j.talanta.2008.12.051