Parkinson and statins

New research points to a possible link between the LDL cholesterol-lowering statin drugs (HMG-CoA reductase inhibitors) and Parkinson’s disease. Such is the concern that a study involving thousands of people is planned to assess the risk, according to a report in Chemistry & Industry today.

Earlier research had hinted at a putative link between Parkinson’s disease and statins, but the latest results from a study linking low LDL cholesterol itself to PD provides the strongest evidence to date that the link could be real.

Researchers at the University of North Carolina say that patients with low LDL cholesterol levels are more than three and a half times as likely to develop Parkinson’s disease as those with higher LDL levels.

Study leader Xuemei Huang told C&I: “I am very concerned by these findings, which is why I am planning a 16000-patient prospective study to examine the possible role of statins.” Huang was quick to point out, however, that a causal link with statins had not yet been proven. Huang adds that the well-established link between PD and apoE2, a gene associated with lower LDL cholesterol, supports her theory that low LDL is the culprit in many cases of PD.

Yoav Ben-Shlomo, a professor of clinical epidemiology at the University of Bristol suggests a contrary explanation. It could be that low LDL cholesterol levels are a consequence rather than a cause of PD, he says.

Nevertheless, statins have been in common use for more than a decade and Huang worries that if proved right we will see a big surge in the number of diagnoses of PD during the next five years.

Pfizer’s statin Lipitor is the world’s best-selling drug with $12.2 billion in sales in 2005.

Solvent abuse

Adolescent drug use has fallen overall since the late 1990s, but the “recreational” use of solvents is on the increase. Solvent, or inhalant, abuse is now the fourth most abused drug among US teens according to NIDA.

Inhalants, which include volatile organic compounds such as butane and aromatic hydrocarbons (like toluene) activate the same areas of the brain as do other drugs of abuse. However, understanding their precise mode of action has not been clarified until now.

Toluene is found in paint thinners, varnishes and even nail polish remover and is commonly abused and new research shows that it stimulates dopamine release in specific regions of the brain known as drug reward pathways. The results, obtained by Arthur Riegel and colleagues at the Vollom Institute, in Portland, Oregon, suggest that the brain interprets inhalation of toluene as a rewarding experience which can result in continued abuse and re-abuse.The findings could help in developing strategies to prevent and treat addiction to substances containing toluene.

Surprisingly, researchers also found that toluene-containing substances are most effective at low concentrations. Since toluene is rapidly absorbed by the brain, this might explain why the preferred mode of delivery is by “huffing” or “sniffing”. Sniffing is frequently considered a harmless recreational or party drug but unlike other drugs, even a single session of inhaling the compound can disrupt heart rhythms enough to cause cardiac arrest and lower oxygen levels enough to cause suffocation. Not a good thing.

The research is published today in the journal Neuropsychopharmacology.

Obesity and colon cancer link

Obesity is a major risk factor for colon cancer, but until now medical scientists were at a loss to explain why. Now, a study of on three human colon cancer cell-lines has demonstrated that the “fat hormone” leptin may enhance the growth of colonic cancer cells. The discovery not only offers an explanation as to the underlying cause of the increase colon cancer risk in obesity but could lead to a new approach to fighting this type of cancer.

The hormone leptin is released by fat cells, adipocytes, so the higher your body fat content (calculate your body fat now), the higher the concentration of leptin in your blood stream is likely to be. Leptin plays a key role in regulating metabolism, body weight and energy expenditure.

According to previous research, people who are obese are two to three times more likely to develop colon cancer than their leaner counterparts. Other research revealed that some colon cancer cells carry receptors for leptin.

Now, scientists at the University of California San Diego School of Medicine believe they have found the link.

“These results may explain why obesity increases a person’s risk of colonic cancer, and the fact that we have shown how leptin stimulates these cells means that drug companies may be in a better position to develop new treatments against the disease,’ says UCSD’s Kim Barrett.

The team grew cancer cells in the laboratory and found that leptin could stimulate their growth. In two out of three cell lines, leptin also blocked normal programmed cell death, apoptosis, which usually prevents runaway cell growth. When apoptosis fails normal cells can become cancerous.

The researchers explain that they have also found the complex chemical signalling pathways in the cell that are influenced by leptin, which reinforces their claim that leptin does indeed play a critical part in influencing cancer cell growth in the colon.

The results are published in detail in the journal BJS.

Two for tea

Two tea time stories in the news today. The first reports on a very small study showing that adding milk to tea negates the cardiovascular health benefits because it interferes with nitric oxide (NO), the natural vasodilation controller (You’ll know it from my article on Viagra. The second news item is about the antibacterial effects of green tea (it doesn’t say whether adding milk negates those benefits, but I cannot imagine drinking green tea with milk anyway.)

New York Smells

Today, the New York City authorities were investigating a persistent smell of “gas” across a large part of the lower Manhattan area of the city.

Hundreds of people reported the odd, but apparently not noxious smell, to the New York Police Department, but at the time of writing the identity of the gas remained unknown. Despite this, Mayor Michael Bloomberg somehow manages to make confident proclamations that the gas is “not dangerous”.

Over on Digg, a heated debate has been raging since the first news of the mystery smell was released on an unsuspecting public. Some members of the so-called online “news” community, claim to live in NYC and that there is no smell. Others muse that Howard Stern is to blame, while yet others are confused as to whether this represents a homeland security issue.

Some New Yorkers are saying the gas smells of gasoline (petrol to those of us this side of the pond), while others reckon it’s more like natural gas (methane, of course, has no odour so a very strong smelling sulfur-containing compound – mercaptan – is added in tiny amounts to give it a smell).

The BBC reported that the source was across the Hudson River in New Jersey, where officials said a natural gas leak originating in the Chelsea district of Manhattan, had occurred.

New York, new york, so good they named it twice…

Scratchy and itchy

Researchers are only just begin to scratch the surface of the brain with functional MRI. Now, a study of perception in both allergen- and histamine-induced itch has revealed how different parts of the brain are activated in response to stimulation from each type.

Allergens, such as pollen and dust, and histamine released by allergy cells as a result of activation by foods, drugs, or infection often lead to a vicious itch?scratch cycle as any allergy sufferer will tell you. However, researchers at Oxford University have demonstrated that the brain responds differently to itchiness caused by allergens and histamine.

Siri Leknes, Susanna Bantick, Richard Wise, and Irene Tracey at Oxford have worked with Carolyn Willis and John Wilkinson of the Department of Dermatology, at Amersham Hospital to try to understand the nature of itch? cycle with a view to improving outcomes for allergy sufferers and people with certain chronic skin conditions.

Read on in the latest science news round-up from David Bradley on spectroscopynow.com

Drugs and addiction

Fly agaricMany people in the modern Western world delude themselves that their culture is generally free from the effects of intoxicating substances except in the criminal underworld, and that ‘nice people don’t take drugs’. But Richard Rudgley of the University of Oxford, a researcher of the oasis communities of Chinese Central Asia, shows that our culture and other cultures across the world have a rich tradition of using chemicals, mainly from plants, to produce altered states of consciousness. These range from the ritualistic use of the fly-agaric in Palaeolithic Europe to betel-nut chewing in Papua New Guinea, and from pretentious bone-china tea sets in Surbiton to the tragic inhaling of petrol fumes by Aboriginal Australians.

Although each intoxicant has its own effects on the mind – there is some overlap – but researchers have classed them as belonging to four types. Hallucinogens – compounds such as mescaline – are often found in ‘poisonous’ varieties of mushroom or South American weeds. Inebriants consist of generally simpler organic compounds such as alcohol, and the constituents of organic solvents and other volatile chemicals. Hypnotics are compounds that induce states of sleep, stupor or calm and include tranquilizers and narcotics. Stimulants increase mental activity and include caffeine, tobacco and the more potent cocaine and amphetamines.

Rudgley has scoured the scientific literature for examples and evidence from the European Stone Age to modern day Australia to improve our understanding of how these broad classes of intoxicants have affected society and religion. Beginning with evidence from the earliest days of hallucinogen use in Palaeolithic cave art, Rudgley describes in fascinating detail intoxicants and their cultural effects over the past few thousand years.

For example, peyote, the mescaline-containing cactus of Texas and Northern Mexico, apparently played an important role in the cultural development of indigenous peoples of that area, although the plant is now threatened with extinction because of increasing use by modern hedonists. On the Steppes biochemical evidence shows that Cannabis sativa and ethanol have been commonly used for many thousands of years.

Rudgley even has an explanation for the supposed flight of witches and the symbolism of the witch’s broom. A witch wanting to ‘fly’ to a witches’ sabbat, or orgiastic ceremony, would anoint a staff with specially prepared oils containing psychoactive plant matter, as well as rather gruesome ingredients such as baby fat and human blood. The potion could then be administered to areas of the body that could absorb the active components most rapidly. Rudgley quotes one researcher: ‘The use of a staff or broom was undoubtedly more than a symbolic Freudian act, serving as an application for the atropine-containing plant to the sensitive vaginal membranes. . .’ So now you know.

There is little spiritualism attached to the modern Western use of intoxicants such as caffeine and nicotine, and society more than frowns on the use of mind-altering drugs. The modern view is perhaps distorted to some extent by the development of highly addictive stimulants such as ‘crack’, with its potentially devastating effects.

Rudgley hopes that a deeper knowledge of intoxicants’ use in other cultures will result in a better understanding of our own culture of cafes and bars, and this in turn might help us understand the ‘importance of altered states of consciousness in both our collective and our personal lives’.

I wrote the original version of this item as a book review that was published in New Scientist magazine (The Alchemy of Culture by Richard Rudgley, British Museum Press, reviewed issue 1909, p43).

The professional staff at an addiction treatment facility knows how to help a drug addict, so you can rest assured your loved one is in good hands.

Christmas rose and hellebrigenin

Structure of hellebrigenin

Members of the plant family Ranunculaceae are ever-popular at this time of year, especially in Europe, where the Christmas rose, Helleborus niger, is wheeled out as a natural decoration for countless households. Interesting then, that extracts of this plant have been used as a heart tonic in herbal medicine alongside the likes of digitalin (from foxglove) and strophanthin from the West African plant Strophanthus gratus.

H. niger contains various potent toxins in addition to cardiac glycosides helleborin, hellebrin and helleborein and saponosides and the ranunculoside derivative, protoanemonine. It was searching for information on the compound hellebrigenin (3-acetate) that brought one Sciencebase reader to this site, so here’s the structure of the molecule. This biologically active compound, which also goes by the name (3beta,5beta,14beta)-3,5,14-trihydroxy-19-oxobufa-20,22-dienolide, is a cardioactive steroid compound as well as having been demonstrated (in the 1960s) to have activity against tumour growth.

More on the Christmas Rose here.

Bird flu non-news

Over on foreignpolicy.com they’re reporting the Top Ten non-News Stories of 2006. Among their picks is the non-story of bird flu, or avian influenza as it’s more correctly known. In case you missed it, we didn’t all die of bird flu again this year. However, there were a few people who, having got so scared of the tiny risk that they might catch the H5N1 strain of the disease began taking Tamiflu prophalactically. More fool them, it turned out. Here’s what the site had to say:

“In November, the Canadian health ministry issued a warning on Tamiflu after 10 Canadians taking the drug had died suspiciously. And the US Food and Drug Administration received more than 100 reports of injury and delirium among Tamiflu takers for a 10-month period in 2005 and 2006. That’s nearly as many cases as were logged over the drug’s five-year trial period. For now, the cure seems worse than the disease.”

Highly ironic that a drug taken for its protective effects against a disease that doesn’t really yet exist should have claimed so many victims. Unless we see a sudden spate of bird flu infections in the developed world, 2006 will remain another year in which none of the scaremongerees actually died of bird flu.

Influenza’s long tail

A long protein tail found in all influenza A virus raises the possibility of novel drugs that can grab on to it and stop the virus in its tracks. The protein tail is present in common human influenza A which kills thousands of people every year as well as rare forms such as bird flu.

US scientists used crystallography to study the long flexible tail of the influenza virus’ nucleoprotein. They found that even seemingly insignificant changes to the structure of this protein tail prevent it from fulfilling a key role in viral replication. That is, they prevent them from linking together to form structural columns used by the virus to transmit copies of itself.

More…