Category: Biology

Touch Wood – Short History of Viagra

Just a reminder that the Sciencebase archive of science articles is stuffed full of interesting tid-bits (to use the PC term). Among the most popular pages (attracting the most readers in other words) is the repro of a feature article I wrote some time ago for Tomorrow’s World magazine on the subject of Viagra.

Said item was illustrated with a large banana and two strategically placed apples. I was going to dig out the original paper cutting and scan it for this item, but didn’t fancy getting a search engine rude-filter slapped on the page.

The Viagra article is here.

Zoo Poo

This is one of those lovely science stories that is sure to catch even the tabloid media’s attention as well as give people the opportunity once again to complain about “what scientists do”.

According to CSIRO Livestock Industries scientist Andre-Denis Wright, droppings from rhinos and elephants at Perth Zoo are being put under the microscope to help scientists determine whether or not various strains of protozoa, which help break food down in the guts of “exotic” animals can be introduced into the guts of sheep and cattle to help them thrive in the harsh conditions of the Australian outback.

As part of the Zoo-Poo project scientists have so far sequenced the DNA of protozoa found in a range of faecal samples from rhinos, elephants, orangutans, and red pandas. The study will reveal the origins of various protozoa and identify common protozoal species found in animals from different parts of the world.

Wright is collaborating with rumen microbiologist Burk Dehority of Ohio State University. Dehority has previously found some of the same protozoa in different grazing animals from South America, Africa and Alaska. However, the protozoa from the guts of marsupials in Australia appear to be quite distinct. He has now received poo samples from the zoo animals including a “grab sample of faeces” from a rhino, collected by a zoo handler before it hit the ground. [Nice]

“Very large mammals like the rhino and the elephant eat voluminous amounts of roughage and they are able to take the soluble nutrients out and ferment them in the cecum and then they just pass the roughage out,” explains Dehority, “hey exist on the fact that they just eat volumes.”

He said little was known about how the guts of large animals worked and the research would assist in developing better nutrition for zoo animals as well as livestock.

Phylum Arthropoda

A common search carried out by sciencebase visitors is “Phylum Arthropoda”. Innocent enough, of course, there are bound to be lots of followers of the site interested in insects, arachnids, and crustaceans.

Anyway, the best starting point to get plenty more info on the arthropods is, as usual, Wikipedia. But, if you’re after science lessons on arthropods then check out the K5 science lesson plans page and follow the link to the Columbia Education Center in Portland, Oregon, to get to the specific listings. If you’ve got a particular creature in which you’re interested, please use the sciencebase search box top right, we can’t guarantee that you’ll find what you’re looking for among the sciencebase pages themselves but there are usually other links on the site you can follow to find out more.

Bremelanotide MSDS

Readers interested in sexual chemistry will have spotted the recent item on bremelanotide (Sex Gets Up Women’s Noses, April 24, 2006), which is soon to enter Phase III clinical trials for female sexual dysfunction (see also PLoS Medicine on the subject of disease mongering).

Anyway, recent sciencebase visitors have been trying to locate the material data safety sheet (MSDS) for this compound (judging from the recent spate of searches on the site for that term). Anyway, ChemSpy.com has excellent access to several MSDS sources here. If it’s listed anywhere you should be able to find the bremelanotide MSDS there.

A blogger on another site discussing my short bremelanotide article, suggested that the fact this drug is odourless and colourless represented a serious risk in terms of men spiking a woman’s drink, but I wonder…this drug doesn’t knock you out or give you amnesia it just makes you horny, so if Mr B. Nomates can’t score under normal circumstances when any number of potential mates may be horny or not, it won’t seriously boost his chances will it?

Turning Sperm Heads

Size really does matter! In fact a micro device that can analyse even the smallest of the small could help solve one of “man’s” greatest mysteries – what turns a sperm’s head and sends it in the direction of the egg for that fertilizatory encounter?

Sperm are well-known for turning their microscopic heads and changing direction (at least to those with a microscope who like to view such tiny events). Previous research (about which I wrote in 1991 under the heading “Not every sperm is sacred”) revealed that sperm turn in response to chemical signals, a process termed chemotaxis, and even have their own olfactory receptors. Such chemical messages may play key roles in the fertilization process. Defects in sperm chemotaxis may be a cause of infertility, and sperm chemotaxis could potentially be used as a diagnostic tool to determine sperm quality to treat male infertility.

However, Milos Novotny and Stephen Jacobson of Indiana University have developed a new tool to probe exactly how sperm chemotaxis occurs. In the current issue of Anal Chem, they describe the initial tests on their microfluidic device for studying sperm chemotaxis: “An advantage of the microfluidic platform over conventional chemotaxis assays is the ability to create chemical gradients with temporal and spatial stability, leading to greater repeatability in the experimental conditions.”

They add that microfluidic devices provide a convenient, disposable platform for conducting chemotaxis assays.

http://dx.doi.org/10.1021/ac052087i

Sex Gets Up Womens Noses

Spray-on sex could usher in an age of McNookie, according to an article in The Observer on Sunday. PT-141 is billed as libido in an atomiser, says the paper, and could finally offer women the chance to turn on their sexual desire as and when they need it.

“A dose of PT-141 results, in most cases, in a stirring in the loins in as little as 15 minutes,” reports Julian Dibbell, “Women, according to one set of results, feel ‘genital warmth, tingling and throbbing’, not to mention ‘a strong desire to have sex’.”

So, what is PT-141?

It’s an odourless and colourless synthetic chemical that you inhale deeply through a small, white plastic inhaler. The compound, produced by Palatin Technologies and currently undergoing regulatory assessment, is a melanocortin-based therapy that seems to work directly on the brain rather than simply stimulating the loins as is the case with Viagra.

The drug’s market name is Bremelanotide and it’s a word you’re sure to see a lot more of in the near future as spammers start offering it and variations on the theme (watch out for Bremelan0tide in your email subject lines). Its mode of action is poorly understood, but unlike thousands of years of rhino horn, tiger dick, and oysters this one definitely seems to work.

Molecular structure of Palatin's PT-141 (Bremelanotide)

“It’s not merely allowing a sexual response to take place more easily,” Michael Perelman, co-director of the Human Sexuality Program at New York Presbyterian Hospital and a sexual-medicine adviser on the PT-141 trials explains, “It may be having an effect, literally, on how we think and feel.” What is known is that it acts on at least one of five known melanocortin receptor subtypes in the brain. These are chemical receptors that regulate a diverse array of functions including sexual arousal, appetite, energy maintenance and inflammation. The company is working on drugs to affect these receptors and so help with sexual dysfunction, obesity and cachexia (disease-related muscle loss).

One has to wonder though whether the advent of drugs like PT-141 is simply another example of the kind of drug mongering I discussed a few years ago my Alchemist column on ChemWeb. There now seem to be dozens more “diseases” than there ever were. Is it just coincidence that problems that were not considered problems are now categorised as syndromes and disorders have emerged at just the time when the patents are expiring on the billion dollar staples of the pharmaceutical industry? Maybe, maybe not. Some of those disorders, such as restless legs syndrome, may sound like spurious ailments invented by a desperate industry, but they certainly aren’t for those who suffer from them. Even shyness and anxiety might one day succumb to drugs, and why not? If these disorders are debilitating then who are we to suggest that sufferers have no right to a treatment that “cures” them?

Sometimes there is no relief for a whole range of problems without pharmaceutical intervention. Whether or not we should allow people the option to control their sexual desire chemically is a moot point, the fact is humans have used all kinds of methods to loosen up a libido for millennia, and will continue to do so whether that’s with a regulated drug or something else. Palatin seems simply to be hoping to take a slice out of the action.

Anyway, for those interested in such things Palatin gives the basic structure of its product as a short cyclic peptide with the sequence – Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH. It’s currently in Phase III clinical trials, so it shouldn’t be too long before those spams start arriving.

Terrorist Detector

Researchers in the US have developed an exquisitely sensitive test, better by a thousand-fold than previous efforts, for detecting trace quantities of cholera and botulinum toxins. These two agents are considered potential agents of a bioterrorist attack. Their test takes just three hours to provide a result.

Until now, the most rapid and sensitive approach to biotoxin detection has involved coupling the polymerase chain reaction (PCR) with antibody specificity for toxins.

To boost the sensitivity of this approach, Jeffrey Mason and colleagues at the Armed Forces Institute of Pathology, Rockville, MD, package about sixty molecules that initiate PCR into a hollow liposome decorated with receptors for the toxin. When present, the toxin binds to the receptors, and when the liposome is subsequently broken open, the released PCR-initiating molecules amplify the signal and enable detection of vanishingly small amounts of toxins – they are detectable even against a background of harmless components in urine and runoff water.

The team reports details of its new test in Nature Biotechnology today.

Pox Virus Undressed to Make its Entry

Geoffrey Smith of Imperial College London and colleagues have discovered how Vaccinia, the smallpox vaccine, enters cells and causes infection. The findings shed light on a novel mechanism by which active pox viruses can infect people. Apparently, the Vaccinia virus sheds its outer lipid membrane to enter cells. This naked entrance mechanism is unique in virology and could pave the way for a range of new antiviral drugs.

Many viruses, such as the H5N1 avian influenza virus, are surrounded by a single lipid membrane, or envelope. To enter cells this membrane has to be shed. Previously, all enveloped viruses were thought to shed their lipid membrane by fusion with a cell membrane which allows the viral core to be released into the cell.

In contrast, the extracellular form of Vaccinia virus has two lipid membranes, meaning a single fusion event will not release a naked virus core into the cell. The Imperial team has found that interactions between negatively charged molecules on the cell surface and sugar-linked proteins, glycoproteins, on the virus’ surface split the virus outer envelope without fusing, allowing the poxvirus to enter the cell.

As well as discovering how the double membrane problem is solved, the researchers demonstrated that these multiply charged, polyionic, compounds can destroy the poxvirus even days after infection has started. Disrupting the outer membrane with polyanionic compounds exposes the virus, allowing antiviral antibodies to be more effective. The disruption of the outer membrane also limits the spread of the virus in the body.

“This work has uncovered a completely novel biological process,” Smith, “It increases our understanding of how viruses can manipulate biological membranes and will help the development of new drugs against poxviruses, such as variola virus, the cause of smallpox.”

Details in Proc Nat Acad Sci

When Clinical Trials Go Wrong

The journal Nature reports on a novel theory as to why trials of monoclonal antibody drug TGN1412 went badly wrong and left six men critically ill with massive organ failure and inflammation in March.

As Sciencebase has already reported, it seems there is no evidence of drug contamination, dosing problems, meaning the devastating effects were almost certainly caused by TGN1412 itself. So, why didn’t this show up in the preclinical animal trials?
Antibodies to be used as drugs are modified to have the same overall structure as a human antibody. The CD28 antibody receptor — which switches on immune cells, and was targeted by TGN1412 — is identical in humans and monkeys, so researchers thought that the drug would have comparable effects in the two species.

But crucially, the antibody’s ‘tail’, at the opposite end of the molecule from the CD28-binding site, may not be the same. Antibody tails are known to undergo a phenomenon called ‘crosslinking’, in which they bind to other antibodies and amplify the immune response. Some researchers believe this could have caused the human volunteers’ immune system to release a massive flood of inflammatory molecules called a ‘cytokine storm’, causing their organs to shut down within hours of taking the drug.

Thomas Hünig, co-founder of the company TeGenero, which developed the drug, told Nature that he agrees this could be what happened. The idea is supported by research on another super-antibody that activates the immune system in a similar way. Early tests in mice triggered an uncontrolled immune response. But tweaks to the antibody’s tail solved the problem, and the drug has now been approved for patients taking immunosuppressive drugs.

Nature

Bird Flu Poll

H5N1 at last reached British shores this month and now both the Eastern and Western seaboards of the USA are on tenterhooks. In the spirit of serious scientific debate, I’ve posted a poll all about avian influenza on the SciScoop Science Forum.

So, are we all doomed to be tarred and feathered or is it just a load of media fluff and feathers? You decide.Meanwhile, check out SciScoop regular contributor Chad’s excellent ongoing posting on the bird flu story on SciScoop.