Tobacco-derived compound prevents memory loss in Alzheimer's disease mice

Cotinine, a compound derived from tobacco, reduced plaques associated with dementia and prevented memory loss in a mouse model of Alzheimer's disease, a study led by researchers at Bay Pines VA Healthcare System and the University of South Florida found. The findings are reported online in the Journal of Alzheimer's Disease in advance of print publication.

"We found a compound that protects neurons, prevents the progression of Alzheimer's disease pathology, enhances memory and has been shown to be safe," said Valentina Echeverria, PhD, a scientist at Bay Pines VA Healthcare System and an assistant professor of Molecular Medicine at USF Health. "It looks like cotinine acts on several aspects of Alzheimer's pathology in the mouse model. That, combined with the drug's good safety profile in humans, makes it a very attractive potential therapy for Alzheimer's disease."

While the current drugs for Alzheimer's may help delay the onset of symptoms, none halt or reverse the processes of Alzheimer's disease. In addition, existing drugs may have undesirable side effects.

Some epidemiological studies showed that people who smoke tend to have lower incidences of Parkinson's disease and Alzheimer's disease. Studies have widely attributed this apparently beneficial effect to nicotine, which has been reported to improve memory and reduce Alzheimer's-like plaques in mice. However, nicotine's harmful cardiovascular effects and addictive properties make the compound a less than ideal drug candidate for neurodegenerative diseases.

The Bay Pines VA/USF team decided to look at the effects of cotinine, the major byproduct of nicotine metabolism, in Alzheimer's disease mice. Cotinine is nontoxic and longer lasting than nicotine. Furthermore, its safety has already been demonstrated in human trials evaluating cotinine's potential to relieve tobacco withdrawal symptoms.

The researchers administered cotinine daily for five months to young adult (2-month-old) mice genetically altered to develop memory problems mimicking Alzheimer's disease as they aged. At the end of the five-month study, the Alzheimer's mice treated with cotinine performed better on tasks measuring their working memory and thinking skills than untreated Alzheimer's control mice. Long-term cotinine treatment appeared to provide the Alzheimer's mice complete protection from spatial memory impairment; their performance in this area of testing was identical to that of normal mice without dementia.

The brains of Alzheimer's mice treated with cotinine showed a 26-percent reduction in deposits of amyloid plaques, which are a hallmark of Alzheimer's disease. Cotinine also inhibited the accumulation of the amyloid peptide oligomers – a predecessor of senile plaques – in the brains of these mice. Furthermore, the researchers discovered that cotinine stimulated the signaling factor Akt, which promotes the survival of neurons and enhances attention and memory.

Senile plaques likely had not yet formed or were just beginning to accumulate in the brains of the young adult mice when long-term cotinine treatment was started. The researchers suggest that "cotinine may be useful in preventing cognitive deterioration when administered to individuals not yet exhibiting Alzheimer's disease cognitive impairment or those with mild cognitive impairment at early stages of the disease."

The researchers are seeking additional support for a pilot clinical trial to investigate cotinine's effectiveness in preventing progression to Alzheimer's dementia in patients with mild cognitive impairment, Echeverria said.

The VA-USF team is also studying the potential of the tobacco-derived compound to relieve fear-induced anxiety and help blunt traumatic memories in mouse models of post-traumatic stress disorder.

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Scientists can track origin of shark fins using 'zip codes' in their DNA

An international team of scientists, led by the Institute for Ocean Conservation Science at Stony Brook University, has used DNA to determine that groups of dusky sharks (Carcharhinus obscurus) and copper sharks (Carcharhinus brachyurus) living in different coastal regions across the globe are separate populations of each species. Both are large apex predators that are heavily exploited for the shark fin trade, which claims tens of millions of animals every year to produce the Asian delicacy, shark fin soup. Many of these species are declining as a result of this fishing pressure for their fins. The dusky shark is classified as "Endangered" in the Western Atlantic by the International Union for Conservation of Nature as its population is below 20 percent of what it was two decades ago. These new studies show that the genetic differences among populations of these sharks are large enough for scientists to be able to track the actual origin of the fins on sale in Asian markets, enabling better regional monitoring and management of these threatened predators.

These research findings appear in two scientific articles. "Global phylogeography of the dusky shark, Carcharhinus obscurus: implications for fisheries management and monitoring the shark fin trade," has been published online in the journal Endangered Species Research. "Phylogeography of the copper shark (Carcharhinus brachyurus) in the southern hemisphere: implications for the conservation of a coastal apex predator" will soon be published in the journal Marine and Freshwater Research. The primary objective of these studies was to identify any genetic differences among regional groups of dusky and copper sharks and establish how many distinct populations there are. The second objective was to determine if these population differences were great enough to allow scientists to reconstruct their contributions to fin trade in the future. Like many large sharks, these species have a wide distribution around the globe but are tied to coastal areas for reproduction.

"By analyzing part of the genome that is inherited solely through the mother, we were able to detect differences between sharks living along different continents – in effect, their DNA zip codes," said Dr. Demian Chapman, leader of the research team and assistant director of science of the Institute for Ocean Conservation Science. "This research shows that adult females faithfully give birth along the continental region where they were born. If fished too much, the population will collapse, and it is extremely unlikely that it will be replenished from immigration of sharks from another region."

This is precisely what has happened along the U.S. Eastern Seaboard, where the once common dusky shark is now rare and a species of concern for listing under the Endangered Species Act. At one time, these animals were common in ocean waters off the United States; however, a recent stock assessment of the sharks along the U.S. East Coast and in the Gulf of Mexico showed an 80 percent decline even though they have been protected since 2000. The recovery of the species is extremely slow because the average age of maturity is 20 years, its reproductive cycle only occurs every three years – including a two-year pregnancy – and its litter size is relatively small (three to 14 offspring).

"Here in the United States, it took only a few decades to nearly wipe out our dusky sharks, and it will probably take a few centuries for their stocks to be replenished," said Martin Benavides, lead author of both studies and research assistant at the Institute for Ocean Conservation Science. "Our results dash any hopes that dusky sharks from other areas of the world will replenish the depleted U.S. stock. The sight of a dusky shark swimming off our shores will be a rare experience for generations to come."

"We know very little about the shark fin trade, but by using DNA-zip coding we can identify source populations that are contributing most to the trade, and prioritize them for management," added Dr. Chapman. "We, therefore, really need to establish sampling programs of fins on their way to Asia or in the markets to regulate the global trade before many more populations suffer the fate of the dusky shark in the United States."

For years, it was difficult to determine the origin of these fins and whether they were from threatened species. A study by Dr. Chapman, which was published in 2009 , used DNA testing to trace scalloped hammerhead shark fins from the Hong Kong market all the way back to the sharks' geographic origin and found many came from collapsed Western Atlantic populations.* These new research results demonstrate that this type of testing also can be used to trace the origins of the fins of dusky and copper sharks.

"As apex predators at the top of marine food webs, it is essential for ocean health that we take steps, such as monitoring and regulating the fin trade, to protect these large sharks," said Dr. Ellen K. Pikitch, executive director of the Institute for Ocean Conservation Science.

Both research projects were conducted by a collaborative international team of scientists from the United States, Australia, South America, Asia, New Zealand and southern Africa. The scientists collectively analyzed part of the mitochondrial DNA in nearly 400 sharks sampled from all over the globe.

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Swiss-US team finds indigenous cases of leprosy in the Southern United States

Using advanced DNA analysis and extensive field work, an international research team has confirmed the link between leprosy infection in Americans and direct contact with armadillos. In a joint collaboration between the Global Health Institute at EPFL in Switzerland and Louisiana State University, clear evidence was found that a never-before-seen strain of Mycobacterium leprae has emerged in the Southern United States and that it is transmitted through contact with armadillos carrying the disease. The results will be published on April 28th in the New England Journal of Medicine. There are only around 150 cases of leprosy in the United States each year. Most of these victims have worked abroad in areas in which leprosy is endemic, making it likely that they may have acquired the disease while outside the US. But, to the alarm of health authorities, a third of all patients infected appear to have contracted the disease locally. The hypothesis that the disease is transmitted though contact with armadillos—aside from humans, the only other known carriers of the leprosy-causing bacteria—was confirmed by fine-grained DNA analysis of both armadillo and human samples done at EPFL.

Leprosy bacilli found in armadillos

It has been known since the 1970s that armadillos are potential carriers of the disease, most likely introduced by European immigrants 500 years ago. But the current study shows inter-species contamination and the presence of a unique strain. "There is a very strong association between the geographic location of the presence of this particular strain of M. leprae and the presence of armadillos in the Southern US," explains Stewart Cole, head of the Global Health Institute in Lausanne and world-leader in the field of genomics of leprosy bacilli. "Our research provides clear DNA evidence that the unique strain found in armadillos is the same as the one in certain humans."

The study included 33 wild armadillos known to have the disease and 50 leprosy patients. The new strain of the bacteria, named 3I, was found in 28 armadillos and in 22 patients who reported no foreign residence. The researchers used genome sequencing to identify the new strain and cross check it with other known strains from Europe, Brazil and Asia, and used genotyping to identify and classify the population infected. It became clear that leprosy patients who never travelled outside the US but lived in areas where infected armadillos are prevalent were infected with the same strain as the armadillos. These findings prompted the researchers to state in the article that "Frequent direct contact with armadillos and cooking and consumption of armadillo meat should be discouraged." The study also suggests that armadillo range expansion should be monitored.

It is not known exactly why armadillos contract and carry leprosy. While their low body temperature (89° F / 32° C) makes them perfect incubators for the bacteria, which grow in temperatures between 86° F and 89° F (30° C to 32° C), there are almost certainly other factors such as immune deficiency that also play a role. Similarly, the bacteria attack the extremities of humans because our core body temperature is too high for a generalized infection, and over 90% of humans who come into direct contact with the disease spontaneously fight it off. "The last thing we want is to induce panic in the population and incite a slaughter of armadillos. The best way to combat further infection is though education and prudence," says Cole.

The stigma of leprosy

José Ramirez, a former migrant worker from Houston who contracted the disease after hunting and eating armadillo meat and took part in the study, has consecrated his life to combating social stigmas. He hopes that the study brings to light the stigma attached to leprosy. "We need to take this opportunity to give leprosy patients a voice and to learn to not use the word 'leper' that has negative connotations around the world, a stigma that should be replaced with an understanding of the disease and its causes." Ramirez, who struggled over five years with the disease before it was properly diagnosed, is now disease-free after receiving antibiotic treatment. Proving what few know to be true—that leprosy is a bacterial infection that can be cured.

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Super bug researcher calls for global action

The World Health Organisation (WHO) must take a tougher stance on super bugs, according to a University of Queensland infectious diseases expert.

Professor Tim Walsh, from UQ's Centre for Clinical Research, suggests that bacteria is more widespread than previously thought, with his research published in the Lancet.

The research indicates NDM-1 is present in New Delhi's drinking water and seepage, and thus is widely prevalent in the Indian environment.

Professor Walsh said international efforts were crucial to stem the tide of antibiotic resistant bacteria (known as NDM-1 positive bacteria).

"Along with the fact that some people infected with the new multi-resistant NDM-1 super bugs did not have a hospital stay in India, this research indicates that NDM-1 positive bacteria are occurring on the streets of New Delhi."

Professor Walsh said the research highlighted the urgent need for action to limit the global spread of NDM-1 producing bacteria.

"The potential for the spread of superbugs is real and it is time for an unequivocal international commitment to combat the growing threat," he said.

Only a small number of infections caused by NDM-1 bugs have been detected in Australia, in travellers returning from India.

"At the moment there are five known cases in Australia and at least two in Queensland. Without exception all have been linked to Southern Asia," Professor Walsh said.

Professor Walsh said the study showed there was an urgent need for broad epidemiological and environmental studies to be done, not just in India, but also in Pakistan and Bangladesh, which are source countries for other exported cases of infection.

"There are many good documents written, not least by the WHO, listing key points to curb antibiotic resistance," he said.

"The trouble is that these are merely recommendations which can be adhered to or totally ignored – sadly it is easy to ignore them.

"But we have now reached a point where we can no longer ignore these recommendations and effective measures now need to be enforced.

"A holistic approach and a change of social priorities in various countries is needed, however, it may well be too late to save one of medicine's most precious and long standing resources – antibiotics."

Professor Walsh said screening of hospital transfer patients from India has already been initiated by French, Chinese and Korean health authorities and is being considered in the UK.

The Lancet article – "Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implications for human health: an environmental point prevalence study" – is the first molecular study to look at superbugs in the general environment, rather than a hospital environment.

A group of journalists from Channel 4 News in the UK were central to the research.

They helped collect the seepage and water samples in India for analysis by researchers at Cardiff University, where Professor Walsh was based.

Professor Walsh said he and his colleagues, many based in India, were very keen to facilitate further studies in Southern Asia to help establish key risk factors for acquisition and spread of NDM-1 positive bugs and to identify intervention measures to curb their spread.

Professor Walsh's previous NDM-1 research (also published in the Lancet) revealed the presence of super bugs in hospitals in India, Afghanistan, Bangladesh and their subsequent import into the UK. It influenced international trade, caused a mini-run on Chinese markets and attracted a significant reaction from the Indian government and surgeons.

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Chilli keeps hunger pangs at bay

The latest diet aid comes in the form of capsaicin, which gives peppers their heat and can reduce hunger pangs while increasing energy levels, according to researchers from Indiana.

So does the answer to weight loss lie in our spice cupboard? The study, conducted at Purdue University, suggests a sprinkling of chilli pepper on your supper could help you burn calories faster and curb cravings for fatty, salty and sweet foods.

‘We found that consuming red pepper can help manage appetite and burn more calories after a meal, especially for individuals who do not consume the spice regularly,’ says Professor Richard Mattes.

‘Dietary changes that don’t require great effort to implement, like sprinkling red pepper on your meal, may be sustainable and beneficial in the long run, especially when paired with exercise and healthy eating,’ he says.

Other studies have looked at consuming capsaicin in capsule form, but the latest study suggests that the process of tasting the red pepper actually optimises its effects. Prof Mattes claims the sensory experience maximises the digestive process and increases metabolism.

The six-week study of 25 non-overweight people, published in Physiology and Behaviour, found that the consumption of the red pepper increased core body temperature, therefore burning more calories through natural energy expenditure.

‘The appetite responses were different between those who liked red pepper and those who did not, suggesting that when the stimulus is unfamiliar it has a greater effect,’ say the researchers. ‘Once it becomes familiar to people, it loses its efficacy.'

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Chronic illness is the 'biggest killer', says WHO

The Global Status report said so-called noncommunicable diseases accounted for more than 36m deaths in 2008.

It showed 80% of the deaths were in low and middle income countries.

It said they posed a greater threat than infectious diseases such as malaria, HIV and tuberculosis.

Dr Margaret Chan, WHO Director General, said: "The rise of chronic noncommunicable diseases presents an enormous challenge.

"For some countries, it is no exaggeration to describe the situation as an impending disaster; a disaster for health, for society, and most of all for national economies."

Chronic noncommunicable diseases deliver a two-punch blow to development. They cause billions of dollars in losses of national income, and they push millions of people below the poverty line, each and every year."

The WHO said many of the deaths could be prevented by introducing policies such as promoting healthier diets and stronger smoking legislation.

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Salman's 'Character Dheela' a tribute to Raj, Dilip and Dharmendra

Director Anees Bazmee and superstar Salman Khan say that the song 'Character Dheela' from their upcoming film 'Ready' is a tribute to legendary Bollywood actors - Raj Kapoor, Dilip Kumar and Dharmendra.

In the song Salman and Zarine will be seen paying tribute to these yesteryear actors of Hindi cinema. Both will play different hit movie pairs of the past. "We often use this word 'character dheela hai' in a negative way. We were trying to make it sound good. Eventually the song should look good and presentable. Personally, my character is less 'dheela' as you can see my average is very less...and I am 46-year-old," said Salman.

In one act, both will be seen playing Shahzada Saleem and Anarkali like Dilip Kumar and Madhubala in Mughal-e-Azam; in another act Salman and Zarine will be seen in the black and white era playing tribute to the showman Raj Kapoor along with Nargis. Yet another sequence will see the two recreate the magic of the 'Sholay' pair, Viru and Basanti on screen. "It is our way of paying tribute to Raj Saheb, Dilip Saheb and Dharamji. We are not one per cent close to their performances," Salman said.

The song has been choreographed by Mudassar Khan, who has previously choreographed Salman in 'Dabangg'. "I was an assistant to Raj Saheb in 'Prem Rog'. I respect him a lot. I am a huge fan of Dilip Saheb and Dharamji entertained us a lot. Salman and me love and respect them a lot. So he is in their get up," said director Anees.

"Our intention is not to hurt anyone. They are all our seniors and we have grown up seeing their films and have learnt a lot from them. We have not done anything that would disrespect them and their work towards cinema," he said.

The romantic comedy, starring Salman and Asin, is all set to release on June 3.

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