Higher concentrations of melanin -- the color pigment in skin and hair -- may be placing darker pigmented smokers at increased susceptibility to nicotine dependence and tobacco-related carcinogens than lighter skinned smokers, according to scientists.

"We have found that the concentration of melanin is directly related to the number of cigarettes smoked daily, levels of nicotine dependence, and nicotine exposure among African Americans," said Gary King, professor of biobehavioral health, Penn State.

King states that previous research shows that nicotine has a biochemical affinity for melanin. Conceivably, this association could result in an accumulation of the addictive agent in melanin-containing tissues of smokers with greater amounts of skin pigmentation.

"The point of the study is that, if in fact, nicotine does bind to melanin, populations with high levels of melanin could indicate certain types of smoking behavior, dependence, and health outcomes that will be different from those in less pigmented populations," explained King. "And the addiction process may very well be longer and more severe."

The team's findings appear in the June issue of the journal Pharmacology, Biochemistry and Behavior.

To investigate the factors linking tobacco use, nicotine exposure, and skin pigmentation, the researchers recruited 150 adult African American smokers from three sites in inner city Harrisburg during summer 2007. Participants provided researchers with the average number of cigarettes smoked each day and answered a questionnaire that measured nicotine dependence -- the Fagerstrom Test of Nicotine Dependence (FTND).

Researchers also measured the smokers' cotinine levels. Cotinine is a metabolic byproduct of nicotine that can be used as a biomarker for tobacco use. King and colleagues surmise that nicotine's half-life may, along with tobacco toxicants, be extended due to the accumulation in melanin-containing tissues.

Statistical analyses of data on the three measures of smoking -- cigarettes per day, FTND score, and cotinine levels -- along with a host of other variables including age, education and social demographics of the smokers, reveal that facultative melanin -- the total amount of melanin acquired genetically plus the amount from the tanning effect of sunlight -- is significantly linked to the number of cigarettes smoked per day as well as the FTND score. This link was not observed with constitutive melanin, which is the amount of melanin solely acquired genetically.

However, the Penn State researcher cautions that additional studies with larger samples of smokers with varying levels of skin pigmentation will be required to provide a clearer picture of the link between skin color and nicotine addiction.

"We also think that studies conducted at different times of the year and in different geographic regions would help avoid seasonal variations such as the effect of tanning during summer," King explained. "Additionally, nicotine levels could also be influenced by factors such as consumption of alcohol, amount of exercise, diet, body fat and stress. Future studies will have to control for these factors as well."

Scientists studying the clinical features of 11 sporadic human infections by triple-reassortant swine influenza A (H1) viruses that occurred in the three or so years leading up to the current swine flu epidemic, found that most of the patients had been exposed to pigs directly or indirectly, and that although they all recovered, some of them had severe symptoms, including some who were previously healthy.

The study is the work of Dr Lyn Finelli, head of influenza surveillance at the US Centers for Disease Control and Prevention in Atlanta, and colleagues from state health departments throughout the US, and was published online on 7 May in the New England Journal of Medicine.

Triple-reassortant swine influenza A (H1) viruses have scraps of genetic material from avian, human, and swine influenza viruses. They started to appear in and become native to ("enzootic") pig populations in North America in the late 1990s, said the authors in their background information.

The viruses also infected humans, and for this study Finelli and colleagues examined the clinical characteristics of the first 11 sporadic cases in humans that occurred between December 2005 and February 2009, or up to just before the current epidemic of A/H1N1 in humans.

To study the cases, the researchers looked at reports from national flu surveillance and investigations by public and animal health authorities.

The results showed that:

* The ages of the 11 patients ranged from 16 months to 48 years, with a midpoint (median) at age 10.

* 4 of the 11 patients had underlying health problems.

* 9 of the 11 patients had been exposed to pigs: 5 had been in direct contact and 4 had visited pig facilities but had had no direct contact.

* 1 of the 11 patients was thought to have become infected through human to human contact.

* The incubation period (from last known exposure to start of symptoms) was between 3 and 9 days.

* 10 of the 11 patients had known clinical symptoms that included fever (9 of the 10), cough (all 10), headache (6 of the 10) and diarrhea (3 of the 10).

* Complete blood tests were done for 4 of the 11 patients. These showed that 2 patients had low white blood cell counts (leukopenia), one had a low lymphocyte count (lymphopenia) and one had a low platelet count (thrombocytopenia).

* 4 of the 11 patients were hospitalized, with 2 requiring invasive mechanical ventilation.

* 4 of the 11 patients were treated with the antiviral drug oseltamivir (Tamiflu), and all 11 patients recovered from the influenza infection.

The authors concluded that:

Before the current epidemic of swine-originating flu, there were sporadic infections of triple-reassortant swine influenza A (H1) viruses among humans in the US.

"Although all the patients recovered, severe illness of the lower respiratory tract and unusual influenza signs such as diarrhea were observed in some patients, including those who had been previously healthy," they added.

The CDC said in an announcement on their website this weekend that they expect more cases, more hospitalizations and more deaths as the current outbreak of the novel influenza A (H1N1) continues to expand in the United States in the coming weeks.

The current response strategy is to reduce spread and illness severity, and continue to give up to date information to health care workers, officials and the public.

On Sunday, the CDC reported that the latest number of confirmed lab cases of novel H1N1 virus infections in the US (including the District of Columbia) was 2,532 in 44 states, including 3 deaths.

The CDC has developed a PCR diagnostic test kit that identifies the new H1N1 virus genetically. The kit is being distributed throughout the US, Puerto Rico and other countries.

The authorities anticipate that the number of reported cases will go up as diagnostic capacity increases, which should give a more accurate picture of the spread and extent of the new virus.

A new US study found why a very small proportion of arterial plaques become deadly and lead to heart attack or stroke and why the vast majority others stay benign and apparently do no harm.


The study was the work of researchers at Columbia University Medical Center, and New York University Medical Center, both in New York, and is published in the 6 May issue of Cell Metabolism.

The researchers said that many people are wrong to believe that all arterial plaques inevitably result in heart attack or stroke and their study found out why so few of them are actually worth worrying about.

They also found an important protein that may be responsible for benign plaques turning into dangerous one.

While most atherosclerotic lesions are harmless, only about 2 per cent of them will eventually cause an acute and often fatal blood clot that leads to heart attack, sudden death or stroke, said the researchers.

What distinguishes a dangerous plaque from a benign one is the "billion dollar question" said Dr Ira Tabas, who is Richard J Stock Professor and Vice Chairman of Research, at the Department of Medicine at Columbia University and Professor of Medicine and Anatomy and Cell Biology.

Plaques or atherosclerotic lesions, are fatty, inflamed deposits that form on the inside walls of arteries. These deposits also collect white blood cells known as macrophages and the lesions build up at various spots along blood vessel walls, said Tabas, adding that it is not the size of the deposit but what lies beneath the surface that makes it a dangerous one.

He likened it to the magma or molten lava inside a volcano: rumblings in the core, which in the case of arterial plaques is made of dead cells, can erupt, and once a plaque ruptures it can form a blood clot in the lumen or the interior space of the artery through which the blood flows.

Their finding supports the idea that so-called endoplasmic reticulum (ER) stress together with the body's natural way of coping with that stress is one reason why the rupture takes place.

The ER of a cell does two things: it makes, folds and transports new proteins; and it controls the storage and release of the cell's store of calcium.

When something disturbs the cell's normal operation, it kicks into action a pathway called the unfolded protein response (UPR) which triggers cell suicide in those cells that are particularly stressed. The trigger for cell suicide is an ER stress effector conveniently called CHOP.

Tabas said it's OK for cells to die as long as they don't do so in large numbers. The ER pathway, when it works well, protects the whole organism, killing a a few cells here and there, But more and more scientists are beginning to realize that ER stress and the body's "overexuberant" reaction to it are common features of underlying neurodegenerative disease, aging, and diabetes, he said.

While earlier studies had suggested a link between ER stress and vulnerable plaques, this is the first to show a clear causal link between the two, said Tabas.

"It is this sudden clotting that restricts blood flow and can cause a heart attack, stroke, or sudden cardiac death," said Tabas, explaining that in our modern world most people have atherosclerosis by the time they reach the age of 20, and the challenge for the future will be stopping the harmless lesions in young people from becoming dangerous ones, or as he put it "soothing dangerous plaques so they don't rupture as we age".

Tabas said it was not obvious how to do that yet. There could be many reasons why plaques turn from benign to dangerous, but one of these is definitely linked to the presence of dead cells inside them, the necrotic core as the researchers termed it.

The dead cells release substances that weaken to cap that covers the lesion and hence allow it to erupt and trigger the formation of a clot, said Tabas.

For the study, Tabas and colleagues fed two groups of mice bred to have atherosclerosis a diet high in fat and cholesterol for 10 weeks. One group of mice had the CHOP gene deleted while the other did not. The mice without the CHOP gene produced smaller plaques than those with CHOP. But more importantly, the mice without the CHOP gene also showed 50 per cent lower rates of cell death and plaque necrosis.

Repeating the experiment with another strain of atherosclerotic mice showed essentially the same result, they noted.

Although previous studies have pointed to ER stress and UPR before, Tabas said their result still surprised them, especially the size of the effect.

"The fact that we were able to isolate one gene encoding one protein with such a profound effect on plaque necrosis was a big surprise," he said.

They were surprised because they were expecting this to be just one of many processes at work, including some that might compensate for the loss of the CHOP gene.

Tabas said that finding this effect in mice could translate to real clinical benefits for humans.

The finding opens the possibility that drugs targeting the CHOP gene could silence ER cell stress and be an effective way of treating heart disease, the number one killer in the US.

While cholesterol busting drugs can reduce the number of plaques that deposit inside arteries, they don't work for everyone, and besides, the deposits start quite early in life, with fatty streaks appearing in our arteries in our teens and plaques appearing in our 20s.

"A therapy that prevents the deaths of these cells may be able to reduce the number of vulnerable plaques and prevent heart attacks and strokes in the 70 percent of people who aren't protected from cholesterol-lowering drugs," said Tabas.

However, it might be years before an effective therapy based on this discovery is generally available, said the researchers, but it may be possible to bypass the problem of cell death by persuading other cells inside the plaque to capture and eliminate the dead cells before they can cause eruption.

In the meantime, there is another, well tested way. Although our knowledge of atherosclerosis may be changing, the best option may not, it may still be to have a healthy diet, take plenty of exercise, and keep an eye on cholesterol and blood pressure, said Tabas.

Continuing their groundbreaking research into the treatment of mood disorders in older adults, psychiatrists at the Weill Cornell Institute of Geriatric Psychiatry at the NewYork-Presbyterian Hospital/Westchester Division in White Plains will begin new studies on the effects of quetiapine (Seroquel: Astra Zeneca) and lamotrigine (Lamictal: GlaxoSmithKline). Although both drugs have been approved for aspects of the treatment of patients with bipolar disorder, to date there has been limited research into their effects on older adults with bipolar depression.

The studies are being led by Dr. Robert C. Young, professor of psychiatry at Weill Cornell Medical College, and his colleagues at the Institute of Geriatric Psychiatry. With more than 30 years of clinical and research experience, Dr. Young's focus has been to develop information that can improve the treatment of older adults suffering severe mood disorders.

Dr. Young, an attending psychiatrist at NewYork-Presbyterian/Westchester, said: "To date, most bipolar disorder treatment studies have been conducted in younger patients. In some older bipolar patients a good symptom response is difficult to achieve, and they often have recurring symptoms, disability, multiple medical disorders and increased mortality rates. We hope that findings from these studies will help physicians better manage the care of their geriatric bipolar patients."

Eligible participants must be 60 years of age or older with a diagnosis of bipolar disorder and currently suffering from symptoms of depression. They will be required to meet with a psychiatrist one day per week for a few hours and receive medication management from the treatment team.

Dr. Young and his colleagues are also continuing to lead another study, funded by the National Institute of Mental Health (NIMH) and now in its fourth year, comparing the efficacy of two commonly used mood stabilizers, lithium and valproate, for the treatment of bipolar disorder in older adults. To date, more than 140 individuals in six study sites across the United States including NewYork-Presbyterian/Westchester have participated.

Dr. Young added: "We've heard from some participants in the NIMH study that they have gotten satisfaction in knowing that the findings from this important research may be of benefit to other older individuals -- now and in the years ahead -- who are similarly afflicted with bipolar disorder."

Bipolar disorder involves periods of elevated mood -- mania or hypomania -- and periods of depression, or "mixed" episodes in which patients have both kinds of symptoms. Examples of manic symptoms are high levels of energy, going without sleep for extended periods, elated mood or irritability, and impulsive or reckless behavior. Patients may not recognize that they are having symptoms.

Very low levels of lithium in drinking water may help prevent suicide in the general population, according to a new study.

The study has prompted calls for further research into the possibility of adding lithium to drinking supplies - like water fluoridation to improve dental health.

Researchers at Oita University in Japan measured lithium levels in tap water in 18 municipalities in the Oita region. The lithium levels ranged between 0.7µg/l (micrograms per litre) and 59µg/l.

The researchers then calculated the suicide rate in each of the 18 municipalities. They found that the suicide rate was significantly lower in those areas with the highest levels of lithium in the water.

Writing in the May issue of the British Journal of Psychiatry, the researchers said: "Our study suggests that very low levels of lithium in drinking water can lower the risk of suicide. Very low levels may possess an antisuicidal effect."

Lithium is a naturally occurring metal found in variable amounts in food and water. In medicine, very high doses are used to treat bipolar disorder and mood disorders. But so far the potential benefit of using low levels of lithium to reduce the risk of suicide has not been studied closely.

Vancouver-based psychiatrist Professor Allan Young has described the study as "intriguing".

Commenting on the Japanese study in the same issue of the British Journal of Psychiatry, Professor Young said: "A logical first step would be for the Medical Research Council to convene an expert working party to examine the available evidence and suggest further research.

"Large-scale trials involving the addition of lithium to drinking water supplies may then be feasible, although this would undoubtedly be subject to considerable debate. Following up on these findings will not be straightforward or inexpensive, but the eventual benefits for community mental health may be considerable."