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Smoking Kills Brain Cells

Nicotine can kill brain cells and stop new ones forming in the hippocampus, a brain region involved in memory, says Pier Piazza of France's National Institute for Health and Medical Research (INSERM) in Bordeaux. The finding might explain the cognitive problems experienced by many heavy smokers when they try to quit.

The team allowed rats to self-administer doses of nicotine daily for six weeks. At blood nicotine levels comparable to those found in smokers, they found the creation of new neurons in the hippocampus was cut by up to 50 per cent. Cell death also increased.The implications for smokers and for those using nicotine gum or patches to help them give up are unclear.

Piazza thinks the loss of "neuronal plasticity" could cause cognitive problems, but the team didn?t test this in the rats. "That is the next step. But the hippocampus is involved in memory and neurogenesis seems to be involved in memory, so we might expect there would be an effect," he says.

Short-term cognitive problems in smokers trying to kick the habit are well documented. "But there has been no good explanation for this," Piazza says. "It could be that while they are smoking, the stimulant effect of nicotine masks the loss in neuronal plasticity. When they stop smoking, these deficiencies remain."

Sue Wonnacott, an expert on nicotine at the University of Bath in the U.K. says, "There is a lot of redundancy in the brain and such deficits may or may not be sufficient to account for memory impairments. An alternative view is that memory impairments result from the subject feeling dreadful in the withdrawn state [when they try to quit]."

Exactly how nicotine kills cells is not clear. Previous research on fetal exposure suggest it can induce programmed cell death in immature cells.

Other research has suggested that smoking might actually be beneficial for patients with a variety of diseases associated with brain cell loss because nicotine can attach to receptors for acetylcholine, a neurotransmitter involved in memory. "I don't want to argue with findings that?nicotine?can be beneficial for Alzheimer's," says Piazza. "But now we have found that nicotine can also kill brain cells."

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A once-a-day pill called Iressa that slows cancer by jamming its internal growth signals has been invented. The drug is not yet approved for routine use. It works by interfering only with cancer cells rather than with all fast-growing tissue, as chemotherapy does. As a result, there are far fewer side effects, and patients take it for months or even years.

It?s doubtful that Iressa and drugs like it will actually cure cancer, but they may hold the disease in chec, especially if they?re given in the early stages. "This is a whole new way of treating lung cancer," says Dr. Mark Kris of Memorial Sloan-Kettering Cancer Center. "People didn't think this would work. It's nothing short of amazing."

Kris says the drug eases symptoms quickly. Most patients began to feel better within two weeks. The drug relieved their shortness of breath, coughs, poor appetites and other cancer symptoms. All the people studied had failed to get better after receiving two different regimens of drugs for lung cancer. The volunteers' symptom relief lasted an average of seven months. About one-quarter of the patients enrolled in the study are still alive after 18 months of treatment. The drug's most frequent side effect is an acne-like rash that is usually easy to control.

A similar study was conducted in Europe and Japan on people who were somewhat less sick, because they had failed just one course of chemotherapy. Their tumors shrank in 19 percent of patients, and 39 percent felt better. "It's for real. I can tell you that," says Dr. Roy Herbst of M. D. Anderson Cancer Center in Houston. "I have seen more than several benefit quite significantly"

Studies are also under way to see if Iressa can prevent the development of lung cancer in smokers. The drug is also being studied as a treatment for many other cancers, including breast, prostate and colon.

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A cousin of vitamin A may be able to reverse some of the damage that leads to lung cancer in smokers and maybe even prevent it. People who quit smoking reduce their risk, but the damage caused by tobacco smoke does not immediately stop. Former smokers account for half of all the lung cancer cases in the United States each year.

Doctors have been hoping to find a way to help former smokers reduce their risk of cancer even more. One possible approach uses antioxidants, compounds that can both prevent and in some cases reverse the damage. Some of the most common ones are vitamins A, C and E.

Studies have not shown that taking megadoses of these vitamins can help smokers -- and one study showed smokers who took beta-carotene actually had a higher risk of cancer. So a team led by Dr. Jonathan Kurie of the M.D. Anderson Cancer Center in Houston tried a cousin of vitamin A known as 9-cis retinoic acid that activates genes associated with fighting cancer and has been found to prevent the development of breast cancer in laboratory animals injected with human breast cancer cells.

They tested it on 226 patients who smoked for years but had quit. They were divided into three groups who got either the 9-cis retinoic acid, 13-cis retinoic acid plus alpha tocopherol (a form of vitamin E), or a placebo. Biopsies of their lungs were taken before and after treatments. The researchers were looking for changes in a gene called RAR-beta, which, when active, fights cancer.

Patients given the 9-cis retinoic acid had more activity of RAR-beta, while in patients in the other two groups, the gene became steadily less active. "The 9-cis retinoic acid significantly decreased or reversed the precancerous state, compared to 13-cis retinoic acid or placebo," says Dr. Charles Balch, executive vice president of the American Society of Clinical Oncology. "People who quit smoking are still at risk of lung cancer. Maybe we can reverse some of the damage done by smoking, with very little toxicity." The side-effects included headache, skin rashes and fatigue.

It will take years of follow-up to see if the changes seen in such patients actually prevents cancer. "We have got a long way to go," Kurie says. "We have got to prove the changes in this gene are linked with lung cancer."

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Growing human lung parts for transplant has been brought closer by successful tests in mice performed by scientists from the Imperial College Tissue Engineering and Regenerative Medicine Center at Chelsea and Westminster Hospital in London. For the first time, they have been able to change mouse stem cells into a specific type of lung cell. This means it may one day be possible to regenerate damaged lung tissue.

Right now, the only sure way of addressing terminal lung disease is transplantation from another person, which can give patients an extra 10 to 20 years of active life. But there is a chronic shortage of donor organs and a high risk of rejection after transplantation.

The treatment could also be used for babies born with cystic fibrosis. It will be possible to take some cells from their skin when they?re born, and using growth factor, turn them into lung cells which will be ready by the time the children need them. It?s unlikely that whole lungs can be grown, but it will be possible to grow lobes. Each lung has five lobes.

Dr. Anne Bishop says, "This research will make it possible eventually to repair lungs that have been damaged by disease, by implanting fully functioning lung cells to repopulate damaged areas. Also, unlike transplantation from a donor, the cells can be developed in such a way that the body will not reject them."

Trying to quit? Meditation can help. Learn how by reading ?MindScience? by Charles Tart,click here.

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