Takeda Agrees to Buy Millennium Pharmaceuticals of U.S. for $8.8 Billion
Takeda Agrees to Buy Millennium Pharmaceuticals of U.S. for $8.8 Billion
Takeda Pharmaceutical Co., Japan’s largest drugmaker, agreed to buy Millennium Pharmaceuticals Co.
April 10, 2008
Climate change brings health risks
Climate change brings health risks
“We’re doing everything we can with existing resources now. … With further resources we would be able to do more.”
A top government health official said Wednesday that climate change is expected to have a significant impact on health in the next few decades, with certain regions of the country - and the elderly and children …
Methamphetamine Addiction Mechanism Discovered, Explains Why Cravings Last So Long
Methamphetamine Addiction Mechanism Discovered, Explains Why Cravings Last So Long
ScienceDaily (Apr. 10, 2008) — Repeatedly stimulating the mouse brain with methamphetamine depresses important areas of the brain, and those changes can only be undone by re-introducing the drug, according to research at the University of Washington and other institutions. The study, which appears in the April 10 issue of the journal Neuron, provides one of the most in-depth views of the mechanisms of methamphetamine addiction, and suggests that withdrawal from the drug may not undo the changes the stimulant can cause in the brain.
The researchers set out to determine what sort of changes happen in the brain because of repeated use of the stimulant methamphetamine, and to better understand addiction-related behaviors like drug craving and relapse. Methamphetamine, also known as simply meth, is one of the most popular illegal drugs in the United States, and abuse of the drug can cause severe addiction.
Scientists have believed that abuse of drugs like meth can cause changes to the neurons in the brain and the synapses and terminals that control transmission of information in the brain. In this project, researchers focused on the mouse brain, and how it was affected by methamphetamine over 10 days, which is the mouse equivalent of chronic use in humans.
They found that the long administration and withdrawal of the drug depressed the neural terminals controlling the flow of signals between two areas of the brain, the cortex and striatum. Even a long period of withdrawal — the equivalent of years in humans — did not return the terminals to normal activity level. Re-introducing the drug, however, reversed the changes in the brain.
The areas affected by the drug are called pre-synaptic terminals, and are related to the flow of information from the cortex to the striatum. When a person sees something new in their environment, the scientists explained, she focuses attention on that item. At the neuron level, that process stimulates the release of dopamine, a chemical involved in transmitting signals in the brain. As the person sees the new item over and over again, the dopamine response drops, and synapses in the brain adapt to the no-longer-new item.
What happens with methamphetamine use is that the drug makes the nervous system release dopamine, which helps a user focus a lot of attention on a particular goal. Scientists believe that meth allows dopamine in the striatum to filter information coming from the cortex through the pre-synaptic terminals. The filtering of some of the terminals would help someone ignore other things and focus on that one goal or task.
After chronic use of methamphetamine, the filtering process eventually becomes a permanent depression in the activity of those terminals in the brain, the scientists found. And the only thing that can help the pre-synaptic terminals recover in mice, they found, was re-administering the drug.
"What we found is that the repeated use of methamphetamine causes adaptations in the brain, and that only re-introducing the drug can reverse that," said Dr. Nigel Bamford, UW assistant professor of neurology and pediatrics and a physician at Seattle Children’s Hospital. "We think these changes in the brain may account for at least some of the physiological components of meth addiction."
If the mechanism turns out to be similar in people, Bamford said, this could have big effects on the treatment and management of methamphetamine addiction. One treatment for drug addiction is to give people smaller and smaller amounts of the drug to wean them from it and reduce the effects of withdrawal. Unfortunately, that method would not affect the adaptation of the neural terminals in the brain.
"Now that we have some understanding of the mechanism through which meth addiction occurs, we may be able to develop other approaches to treating addiction," explained Bamford. "We might be able to target some of the chemical receptors in the brain to reset the system and get rid of this depressed state in the pre-synaptic terminals."
Though scientists believe that other stimulants, like methylphenidate, may have similar effects on the brain, they caution against applying these findings to other situations. These synaptic changes may not occur in patients with underlying conditions that require treatment with stimulants, the scientists said.
This research was supported by several grants, including two from the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health. It was also supported by Seattle Children’s Hospital and the Center for Human Development and Disability at the UW. The project included researchers with Columbia University, the New York State Psychiatric Institute, and the University of California at Los Angeles.
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Blood Pressure Enzyme Can Have Tumor-sensing Role
Blood Pressure Enzyme Can Have Tumor-sensing Role
ScienceDaily (Apr. 10, 2008) — By increasing production of a blood pressure-regulating enzyme in mice, researchers have found they can enhance the mouse immune system’s ability to sense tumor growth.
When scientists at Emory University School of Medicine engineered mice that make more angiotensin-converting enzyme in white blood cells called macrophages, the mice could more effectively limit the growth of injected tumors.
The enzyme works by "trimming" small bits of protein that originate from the tumors, allowing the immune system to identify the tumors and mount a response more efficiently.
Senior author Kenneth Bernstein, MD, Emory distinguished service professor of pathology and laboratory medicine, says his group’s findings suggest a strategy for amplifying immune system function in humans. The results are published online in the Journal of Biological Chemistry (JBC).
"We think we’ve discovered a means of tweaking the immune response by modifying the process of antigen presentation," Dr. Bernstein says.
In the clinic, doctors might be able to enhance a cancer patient’s ability to resist a tumor by removing his or her white blood cells, boosting their production of angiotensin-converting enzyme, and re-infusing them, he says.
Antigen presentation refers to how proteins from within the body are constantly recycled and chewed up into small bits called peptides, which appear on the surfaces of cells. While the immune system generally ignores peptides from proteins in the body, it can respond to the peptides from foreign invaders.
Angiotensin-converting enzyme, or ACE, plays a critical role in controlling blood pressure and is the target of common medications. The hormone angiotensin (a peptide) constricts blood vessels, increases the brain’s perception of thirst and indirectly causes the kidneys to retain sodium, thus limiting its production can reduce blood pressure.
ACE acts chemically by removing amino acids, the building blocks of proteins, from one end of a larger protein. In the body, ACE converts an inactive form of angiotensin into an active form by clipping off two amino acids.
But angiotensin is not ACE’s only target. In previous studies, Bernstein and his co-workers found that manipulating its activity also affects processes such as fertility and the generation of red blood cells in the bone marrow.
To dissect out ACE’s role in the immune system, they created mice with a genetic alteration in the ACE gene, forcing the gene to be turned on only in macrophages.
Macrophages are especially good at displaying peptides on their surfaces to other white blood cells called T cells so that the T cells are stimulated to grow. The T cells in turn kill virally infected cells. Depending on the situation, they can sometimes kill tumor cells as well.
When injected with several types of melanoma or lymphoma, the altered mice developed smaller tumors than normal mice. The tumors they did have contained more white blood cells attacking the cancerous cells.
In the JBC paper, the researchers show that ACE boosts cells’ ability to display some foreign peptides, increasing their ability to stimulate T cells by several-fold.
Bernstein cautions that normally, macrophages make little ACE, so its effects must be seen as artificial. He notes that ACE inhibitors such as enalapril and lisinopril are taken by millions of people with high blood pressure and have not been reported to weaken the immune system.
However, cells similar to macrophages have been shown to produce ACE in response to pathogens such as sarcoid or leprosy, he says.
The first author of the paper is postdoctoral fellow Xiao Shen, PhD, with contributions from Aron Lukacher MD, PhD and Ifor Williams MD, PhD, both Emory associate professors of pathology and laboratory medicine.
The research was supported by the National Institutes of Health and the American Heart Association.
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Toni Braxton hospitalized with chest pains
Toni Braxton hospitalized with chest pains
Hello I’m Rebecca Field with today’s UPI entertainment update on this Wednesday, April 9, 2008.
Acute Kidney Injury With Sepsis: A Unique Pathophysiology
Acute Kidney Injury With Sepsis: A Unique Pathophysiology
ScienceDaily (Apr. 9, 2008) — ICU patients with septic acute kidney injury (AKI) are generally sicker, have a higher burden of illness, a greater risk of mortality and longer stays in hospital than patients with non-septic AKI. The findings suggest that septic AKI may represent a unique pathophysiologic condition that may require specific detection and clinical interventions.
Researchers from Melbourne, Australia, evaluated data on more than 120,000 admissions to 57 intensive care units (ICUs) across Australia. Over 33,000 patients had a diagnosis of sepsis, of which 14,000 (42%) had concomitant AKI (septic AKI). Sepsis accounted for 32.4% of all patients with AKI.
Previous research has found that AKI affects more than one third of all patients admitted to ICUs and that discriminating between the septic and non-septic forms of the condition may have implications for how patients are treated.
Compared to non-septic AKI, patients with septic AKI in this latest study had significantly higher acuity of illness, lower blood pressure, higher heart rates, worse pulmonary function, greater acidemia and higher white cell counts.
The septic condition tended to be more severe, with longer ICU and hospital stays and a higher risk of mortality in hospital.
"Septic AKI is common in the first 24 hours after ICU admission," says Sean Bagshaw, who led the study. "Our findings suggest that septic AKI patients are clinically distinct and have distinguishing features and relevant difference in clinical outcomes when compared to those with non-septic AKI.
"Our study further supports the concept that discriminating septic and non-septic AKI may have clinical importance. We now need to investigate further whether patients may require specific interventions, for example mechanical ventilation or vasopressor support, to reduce injury and promote kidney recovery."
Journal reference: Early Acute Kidney Injury and Sepsis: A Multi-Centre Evaluation. Sean M Bagshaw, Carol George and Rinaldo Bellomo. Critical Care (in press)
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Personality Disorders Cause Emotional Reactions In Staff
Personality Disorders Cause Emotional Reactions In Staff
ScienceDaily (Apr. 9, 2008) — A new study suggests that the way in which professional care workers respond emotionally to substance abuse patients with personality disorders depends on the type of disorder.
Birgitte Thylstrup and Morten Hesse of Aarhus University, Centre for Alcohol and Drug Research, in Copenhagen, Denmark, explain that while previous research has shown that antisocial and aggressive behavior in patients can affect how professionals manage them, no previous studies have investigated the distinction between the full range of different personality disorders and their effects on professional health care workers.
The idea that the emotional reactions of a professional to his or her patient may play an important part in psychotherapeutic treatment dates back to the work of Sigmund Freud. He coined the term ‘countertransferance’ to describe the observation that a patient’s influence on the analyst’s unconscious feelings may interfere with the patient’s treatment.
In order to test whether this hypothesis holds for the interaction between health professionals and substance abuse patients, the researchers asked staff members to complete an inventory of emotional reactions to their patients. Concomitantly, the patients, most commonly men in their thirties, were asked to complete a personality disorder questionnaire.
The researchers then sought to determine if there were any correlations between the emotional reactions reported by staff and the type of personality disorder in the patient.
Not unexpectedly, they found that patients with features of antisocial personality disorder induced feelings of distance in their carers. Interestingly, feelings of helpfulness were induced by those with features of avoidant personality disorder.
"The patient with antisocial personality disorder tends to be manipulative and aggressive. It is natural for staff members to react to such behavior with some negative reactions, and this is not a sign of unprofessional conduct", says Morten Hesse. "On the other hand, the patient with avoidant personality disorder is often cautious and appears vulnerable and needy. In that context, many clinicians feel that they can be useful to the patient, and feel secure in their role as treatment providers."
The researchers point out that by using self-reporting, rather than disorders assessed by the staff, they have, for the first time, avoided the problem of a confounding diagnosis. "Staff reactions should be considered in supervision of staff, and in treatment models for substance abuse patients with personality disorders," the researchers conclude.
Journal reference: Substance abusers’ personality disorders and staff members’ emotional reactions. Birgitte Thylstrup and Morten Hesse. BMC Psychiatry (in press)
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Low Birth Weight And Excessive Weight Gain Linked To Heart Problems In Later Life
Low Birth Weight And Excessive Weight Gain Linked To Heart Problems In Later Life
ScienceDaily (Apr. 9, 2008) — Researchers who have followed 5,840 people from before birth to the age of 31 have found evidence suggesting that small size at birth and excessive weight gain during adolescence and young adulthood may lead to low grade inflammation, which, in turn, is associated with an increased risk of developing heart disease.
Previous epidemiological studies have linked environmental factors in early life with the risk of disease in adulthood, and this study identifies a possible causal mechanism. The study underlines the important role of healthy lifestyles, from the foetal period, through childhood, adolescence and young adulthood, in preventing heart problems.
The researchers used a protein called C-reactive protein (CRP) as a marker for general inflammation. CRP is secreted from the liver, is present in blood, and slightly elevated levels can indicate a chronic inflammatory state (low grade inflammation, as opposed to acute inflammation).
"Low grade inflammation is important because it has been associated with future cardiovascular events in many population studies over the past few years and it may play a role in the development of cardiovascular disease," explained one of the authors, Paul Elliott, Professor of Epidemiology and Public Health Medicine and head of the Department of Epidemiology and Public Health at Imperial College London.
Prof Elliott and his colleagues found that when the Finnish participants in the study reached the age of 31, CRP levels were 16% higher per 1 kg lower birth weight, 21% higher per 10cms shorter length at birth, and 24% higher per 1 kg/m3 lower at birth (kg/m3 is known as ponderal index), after adjusting for potential confounding factors. People who were amongst the smallest at birth, but who then put on the most weight up to the age of 31, had the highest average CRP levels. Every extra kg/m2 (body mass index, BMI) gained from the age of 14 to 31 was associated with a 16% rise in CRP levels; this association was greatest for people who had the highest BMI at 14.
Dr Ioanna Tzoulaki, the first author of the study and Lecturer in Epidemiology at the Department of Epidemiology and Public Health, Imperial College London, said: "We compared birth weight of children participating in the Finland 1966 Birth Cohort study with their CRP levels at age 31, and we found that those who had lower birth weight, have higher CRP levels when they are adults, and also the other way round — people who had higher birth weight had lower CRP levels as adults. The ‘lower’ and ‘higher’ CRP levels are relative to measurements in other participants in the study.
"These findings lead us to conclude that small size at birth and excessive weight gain during adolescence and young adulthood may predispose to low grade inflammation, which, in turn, is associated with increased risk of developing cardiovascular disease."
In their EHJ report, the authors say: "The finding that weight gain from adolescence to young adulthood appears to play a greater role in low grade inflammation than weight in adolescence per se, could have important implications for the primordial prevention of cardiovascular disease. Promoting healthier lifestyle in childhood and adolescence, leading to weight stabilisation might be a crucial step in establishing a low cardiovascular risk profile in young adults."
The authors discuss several possible mechanisms and conclude that the results of their study suggest that low birth weight, followed by a greater than average increase in BMI, may trigger the production of the low grade inflammatory response.
Prof Elliott further explained: "Low birth weight has been associated with future cardiovascular diseases and type II diabetes in many studies. This study adds to them and provides a possible explanation for their findings: that this association might be mediated through the effects of birth size on low grade inflammation, as measured by CRP levels.
"There is now ample evidence indicating the importance of the prenatal and early life environment for an individual’s future health, and advice should be given to prospective parents, especially concerning the importance of a healthy diet and the avoidance of exposure to tobacco smoke during pregnancy and childhood — all factors that can impact on the weight of a child at birth. It is also essential that suitable advice is given to children, teenagers and young adults about the effect that excessive weight gain may have on their future cardiovascular health."
Few heart-related problems have appeared among the study participants because they are still relatively young. However, the researchers intend to follow them for at least another 20 years, in order to explore further the associations between small size at birth, weight gain, low grade inflammation and the number of cardiovascular problems that will occur.
Journal reference: Size at birth, weight gain over the life course, and low-grade inflammation in young adulthood: northern Finland 1966 birth cohort study. European Heart Journal, April 10, 2008. doi:10.1093/eurheartj/ehn105
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Just 20 Minutes Of Weekly Housework Boosts Mental Health
Just 20 Minutes Of Weekly Housework Boosts Mental Health
ScienceDaily (Apr. 9, 2008) — Just 20 minutes of any physical activity, including housework, in a week is enough to boost mental health, reveals a large study published ahead of print in the British Journal of Sports Medicine.
While regular exercise is known to be good for mental health, no one seems able to agree on how much, or what type of activity, is best.
The findings are based on a representative sample of almost 20 000 men and women who were quizzed for the Scottish Health Survey about their state of mind and how much weekly physical activity they engaged in.
Over 3000 participants were deemed to be suffering from stress or anxiety, using a validated scoring system.
But any form of daily physical activity was associated with a lower risk of distress, when other influential factors, such as age, gender, and the presence of a long term condition, were taken into account.
The range of activities, which proved beneficial, included housework, gardening, walking, and sports, although the strongest effect was seen for sports, which lowered the risk of distress by 33%.
The results also indicated that while just 20 minutes improved mental state, the more activity a person indulged in, the lower were their chances of psychological distress.
Physical activity curbs the risks of a range of serious diseases, such as heart disease and certain cancers.
And it improves several biological risk factors, such as glucose intolerance and inflammation, which have themselves been linked to depression and dementia, say the authors.
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Does Occupational Success Influence Longevity Among England Test Cricketers?
Does Occupational Success Influence Longevity Among England Test Cricketers?
ScienceDaily (Apr. 9, 2008) — The more test matches a cricketer plays, the longer he is likely to live, suggests research published ahead of print in the British Journal of Sports Medicine.
But captaining the team did not extend lifespan, the findings show.
The researcher wanted to find out if longevity is influenced by a successful career, after taking account of social background, which is known to influence the chances of premature death.
He analysed the length of the lifespan of 418 test match cricketers, playing for England, who were born between 1827 and 1941. Sixty nine were alive at the time of the study.
He found strong associations between survival and year of birth, with perhaps unsurprisingly, players born more recently living longer than those born earlier.
The records differentiated between amateur "gentlemen" and professional players, so providing an indicator of social background.
Amateur "gentlemen" players came from privileged backgrounds, and they lived longer than professional players, who came from working class backgrounds.
Success was measured by the number of test matches in which a player had appeared, with higher numbers of appearances associated with a longer life.
Thirteen per cent of the players had taken part in 25 or more test matches.
A similar proportion had captained the England side at least once. But although this might be considered the pinnacle of success for a cricketer, it had no impact on longevity.
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