Biology – Page 78 – David Bradley

A hearty approach to female sexual dysfunction

Heart drugs are proving rather useful to pharma companies hoping to find lucrative treatments of another kind of disorder, that maybe involves the heart, but mostly involves the loins.

A heart drug that went into clinical trials in the 1990s has become the linchpin for efforts to develop a medication to treat female sexual arousal disorder (FSAD), researchers are reporting. An estimated 40 percent of women have FSAD or another form of female sexual dysfunction, the difficulty or inability to find satisfaction in sexual expression.

Compounds that sustain the activity of vasoactive intestinal peptide (VIP) are a major target of drug research efforts. VIP controls blood flow to the vagina, and decreased blood flow is believed to be one factor in female sexual dysfunction. VIP is degraded in the body by several enzymes, including an enzyme called NEP. Blocking NEP thus allows VIP to continue working.

David Pryde and colleagues at Pfizer in the UK (the company that brought us Viagra) began work with Candoxatril, a powerful NEP inhibitor tested in the 1990s for chronic heart failure. By re-engineering Candoxatril’s molecular structure, they developed a compound with the key actions needed for an FSAD drug.

The new compound blocks NEP, takes effect rapidly, and continues having an effect for a relatively short time. “The compound demonstrates excellent efficacy in a rabbit model of sexual arousal and was expected to be similarly efficacious in humans,” the researchers state in the Journal of Medicinal Chemistry. The compound is undergoing clinical evaluation as a potential treatment for FSAD.

Nitroglycerine and Sex

Nitroglycerine is best known for being the explosive substance you daren’t drop if you’re in a 1950s B movie. But, it also has several medical applications including acting as a vasodilator in the treatment of angina. It was in searching for novel and patentable drugs with similar activity that led to the discovery of Viagra, an experimental drug originally destined for the heart, which found itself pumping blood in an altogether different physiological venue.

Now, nitrogylcerine, or glycerine trinitrate as The Times (London) referred to it yesterday, is set to enter clinical trials as a topical alternative to Viagra and other impotence treatments.

Topical, you say? Doesn’t that mean it has to be rubbed in?

Indeed, Futura Medical in collaboration with GlaxoSmithKline, hope to market a gel that would be applied directly to the penis, cause vasodilation, and that blood pumping we mentioned earlier. The trials will also investigate the effects the gel has on women who share the experience of topical application with a male partner. Why the ladies don’t get their own separate trial The Times does not say. Of course, nitroglycerine is well known for causing headaches, so there’s a little, or big, wedge of irony in any such trial, surely?

Futura and GSK expect the new product codenamed MED2002, for some odd reason, to pass muster with the regulators in 2008 (so why didn’t they call it MED2008?) and be marketed soon thereafter as an over-the-counter, or maybe under-the-counter-in-a-brown-paper-bag, product.

In the meantime, we now have another product for the spammers to add to their list of fake Rx sales, so watch out for spams with subject lines containing – MED2oo2, M@d2002, Medd2002, etc etc, ad infinitum.

Seat of Female Libido Revealed

Over on Digg, there’s news that the organ in the brain responsible for female sexual response has been found. As one might expect, there are lots of sexist comments posting very early and at an alarming rate from the members: Female Libido

The actual news item in question can be found here, written by my good friend at New Scientist, Andy Coghlan.

Owl pellet dissection

A friend of mine is into nature conservation in a big way and one of the tools of the trade, which to the outsider may seem rather odd, is owl pellet dissection. I had a go at dissecting an owl pellet myself, here you can see the results

Owl pellets are the regurgitated remains (bones, feathers and other indigestibles) that accumulate in this bird of prey’s gizzard after it dines on small rodents and other critters. The dessicated pellets are to be found lying where they are discarded by the owl and can provide important information about what critters are being preyed on in owl territory.

The only way to get at that information, however, is to tease apart the pellet with tweezers and other implements to extract the bones from the tangle of hair and other detritus. It needs a steady hand, a keen eye, and a lot of patience. What you will find within is quite amazing though, tiny jaw bones and skulls, femurs, tibias pelvic bones and more.

Identifying which bone belongs to which creature takes even more patience, but it is possible and provides useful insights into the prevalence or otherwise of particular small mammals in a given area where owls prey.

For more on owl pellet dissection, check out this site http://www.kidwings.com/owlpellets/.

The reason I bring it up (pardon the pun) today, is that owl pellet dissection was the hot new search phrase on the sciencebase site this last month, with dozens of visitors all flapping for information on the subject. It’s not a topic that’s been searched for here before, so I thought I’d provide some background in case we have another flutter of en-raptor-ed activity.

Herring Gulls fighting

These two birds I photographed in my in-law’s garden were anything but lovebirds, although they might look like they were dancing seconds before and seconds after they were tearing each other’s feathers off and spitting blood. This didn’t seem to be a bar-room brawl between chums fighting over fishy scraps, these two were at it for a good half an hour. It has to have been a territorial or mating rights argument of some sort.

Nature really is red in beak and claw.

Erotic brain

What a surprise! Medical researchers have discovered that women’s brains light up when they look at erotic images just as men’s brains do.

Researchers at Washington University School of Medicine in St. Louis measured brainwave activity of 264 women as they viewed a series of 55 colour slides that contained various scenes from water skiers to snarling dogs to partially-clad couples in sensual poses.

What they found may seem like a “no brainer.” When study volunteers viewed erotic pictures, their brains produced electrical responses that were stronger than those elicited by other material that was viewed, no matter how pleasant or disturbing the other material may have been. This difference in brainwave response emerged very quickly, suggesting that different neural circuits may be involved in the processing of erotic images.

“That surprised us,” says WUSTL’s Andrey Anokhin, “We believed both pleasant and disturbing images would evoke a rapid response, but erotic scenes always elicited the strongest response.”

As subjects looked at the slides, electrodes on their scalps measured changes in the brain’s electrical activity called event-related potentials (ERPs). The researchers learned that regardless of a picture’s content, the brain acts very quickly to classify the visual image. The ERPs begin firing in the brain’s cortex long before a person is conscious of whether they are seeing a picture that is pleasant, unpleasant or neutral.

Previous research has suggested that men are more stimulated by erotic images than women. Anokhin says the fact that the women’s brains in this study exhibited such a quick response to erotic pictures suggests that, perhaps for evolutionary reasons, our brains are programmed to preferentially respond to erotic material.

“Usually men subjectively rate erotic material much higher than women,” he says. “So based on those data we would expect lower responses in women, but that was not the case. Women have responses as strong as those seen in men.”

So when one sees statistics on net usage that reveal porn accounts for 80% of traffic, it might not just be males who are using up all that bandwidth? Really? Well, I never!

What’s most intriguing though, is that when one searches for the original news release on this item from WUSTL, the cached page in Google shows the context for the phrase “erotic images elicit” as being:

“Attention grabber Erotic images elicit strong response from brain … When study…”

Well, WUSTL press officer, it certainly grabbed my attention. The news release could have done with a few more pictures though!

Sperm and eggs

Adam Bjork and Scott Pitnick of Syracuse University have found a sexy paradox. But, don’t get too excited, it’s fruit fly sex we’re talking here and specifically sperm and egg production in Drosophila.

Previous work in the Pitnick lab showed that after sex, sperm competition takes place within the females (who mate with several males) can lead to decreased sperm quantities by favouring the production of larger sperm. In other words, never mind the quantity feel the length mode comes into play, because female fruit flies have evolved so that longer sperm have a greater chance of successfully fertilizing eggs. Fertilization failure is obviously important as individuals who fail are essentially an evolutionary dead end.

This leads to the ‘big sperm paradox’ because the idea that postcopulatory sexual selection could favour the evolution of giant sperm clashes with traditional sexual selection theory, which predicts that the most successful sperm competitors will be the males that produce many, tiny sperm. As males evolve to produce larger – and therefore fewer – sperm, eggs become less rare, and sexual selection should weaken, according to theory. The term ‘isogamy’ refers to the state at which males and females have equal investment per gamete (sex cell) when producing sperm and eggs. In a truly isogamous population, each sperm and each egg would have a chance to participate in a successful fertilization. In such a population, sexual selection would be extremely weak, as there would be little or no competition among males to fertilize eggs.

To investigate this apparent paradox between empirical data and traditional theory, Bjork and Pitnick set out to measure the strength of sexual selection in four Drosophila species of varying sperm length, ranging from the anisogamous D. melanogaster (in which a male produces 30 sperm in the time it takes a female to make one egg) to the nearly isogamous D. bifurca (where just six sperm are produced per egg). They found that, contrary to theoretical predictions, the level of competition among males did not decrease; the strength of sexual selection remained high as sperm size increased. Their results show that, once females evolve a preference for longer sperm, intense sperm competition can actually reverse the trajectory of sperm evolution so that the most successful males are those with the most female-like strategy of producing very few, large gametes.’The sperm of Drosophila bifurca is 20 times longer than the male that produces it,’ says Bjork.

‘To put that into perspective, if humans made sperm that long and you took a six-foot man and stood him on the goal line of a football field, his sperm would stretch out to the 40-yard line.’

While it is fascinating, the evolution of giant sperm is puzzling. Says Bjork: ‘Until recently, it was widely believed that selection generated by sperm competition favors males that manufacture the smallest gametes possible in order to maximize sperm number. In essence, sperm competition is attributed with the evolutionary maintenance of anisogamy. I became interested in understanding whether the very act of sexual selection, by definition, can limit its own ability to act.’

The next step is to investigate the details of the effects of sperm length evolution on the intensity of sexual selection.

Details were published in Nature under the banner “Intensity of sexual selection along the anisogamy—isogamy continuum”, which doesn’t give much away unless you’re in the field. The paper’s DOI reference number is 10.1038/nature04683. Use our DOI lookup tool to go straight to it (simply cut and paste the DOI and click DOI lookup in the right-hand toolbox) and don’t forget you can grab the simple script to add this and our other toolboxes to your website.

Chirality – panda thumb

The chirality of life, an issue I’ve discussed on numerous occasions in these and other pages, emerges as yet another source of pseudo-science for the intelligent design lobby. Apparently, the bias in handedness among the molecules of life – amino acids, DNA, etc, could not have arisen spontaneously without a guiding hand…

An interesting discussion on this very subject is underway at The Panda’s Thumb blog, it will be interesting to see where it leads. However, my own interviews with chemists on this subject over the years point to a wide range of natural phenomena that could have led to the emergence of the chiral bias with no need to invoke a supernatural hand.

Human to human bird flu

The World Health Organization has expressed concern that a recent cluster of deaths associated with the H5N1 virus in Indonesia may not have originated with an animal host, suggesting the possibility of human to human transmission of the virus. However, it also cautions that the analytical evidence suggests that the virus has not mutated into a human transmissable form, which means we are not just yet on the verge of a global bird flu pandemic after all.

The news media inevitably picked up on this warning and ran with it, but thankfully the BBC saw the double-edged nature of the WHO announcement points out with some degree of rational response that many people in Indonesia, as in other southeast Asian countries, live in such close proximity to their animals and not necessarily in the most hygienic of circumstances that the likelihood of catching bird flu is much higher in such an environment.

It is the lack of a mutated form of H5N1 among these victims that means we are not yet doomed to see the feathers fly globally.

Sex and Vomeronasal Attraction

The vexing question of whether sex pheromones play a role in human sexual attraction raises its ugly head once again, this time in a posting on The Register. Most scientists would say that there is little evidence that humans rely very much on pheromones for sexual attraction directly. However, others scientists suggest that a tiny organ in the nasal cavity, the so-called vomeronasal organ (VNO), or Jacobson’s organ, can detect chemical attractants that pass between people and are not apparent to us at the thinking level. Moreover, anecdotal evidence would point to smell having a very strong effect in sex whether or not we believe it’s pheromonal or not.

The VNO definitely plays a role in the lives of other animals from cats to snakes and from elephants to mice. In humans the organ seemingly all but disappears even before birth, leaving just a few people with a tiny pit in the septum that might have some vestige of pheromonal responsiveness.

Until, we find specific chemicals that trigger sexual attraction when sniffed, in double-blind controlled tests, it is likely that for the foreseeable future there will be no genuine, working product.