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2 different neural pathways regulate loss and regain of consciousness during general anesthesia

University of Pennsylvania School of Medicine researchers have answered long-running questions about the way that anesthetics act on the body, by showing that the cellular pathway for emerging from anesthesia is different from the one that drugs take to put patients to sleep during operations. The findings will be published this week in Proceedings of the National Academy of Sciences.

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Keywords: different, neural, pathways, regulate, loss, regain, consciousness, general, anesthesia, pathway

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1. Advance in understanding of blood pressure gene could lead to new treatments
   02-04-2007 · EurekAlert!
   Research by scientists at UCL (University College London) has clearly demonstrated for the first time the structure and function of a gene crucial to the regulation of blood pressure. The discovery could be important in the search for new treatments for illnesses such as heart disease, the UK's biggest killer. In a paper published online today in Nature Medicine, the team, led by Professor Patrick Vallance and Dr James Leiper, UCL Department of Medicine, reveal the role of the human gene dimethylarginine dimethylaminohydrolase (DDAH), showing that loss of DDAH activity disrupts nitric oxide (NO) production. NO is critical in the regulation of blood pressure, nervous system functions and the immune system. The role of DDAH is to break down modified amino acids (Asymmetric dimethylarginine (ADMA) and monomethyl arginine (L-NMMA)) that are produced by the body and have been shown to inhibit NO synthase. These molecules accumulate in various disease states including diabetes, renal failure and pulmonary and systemic hypertension, and their concentration in plasma (the fluid component of blood) is strongly predicative of cardiovascular disease and death. In a healthy human body, the majority of ADMA is eliminated through active metabolism by DDAH. Scientists have hypothesised that if DDAH function is impaired, NO production is reduced, and that this could be an important feature of increased cardiovascular risk. To examine this pathway in more detail, the researchers deleted the DDAH gene in mice. These mice went on to develop hypertension, or high blood pressure. They also designed specific inhibitors (small molecules) which bind to the active site of human DDAH. These small molecule inhibitors also induced hypertension in mice, confirming the importance of DDAH in the regulation of blood pressure. Dr Leiper, UCL Medicine, said: “These genetic and chemical approaches to disrupt DDAH showed remarkably consistent results, and provide compelling evidence that loss of DDAH function increases the concentration of ADMA and thereby disrupts vascular NO signalling. “There has been considerable scientific interest in this pathway and the role of ADMA as a novel risk factor, but so far there's been little evidence to support the idea that it's a cause of disease, rather than just a marker. Genes and their pathways are crucial to our understanding of cardiovascular disease and a better understanding of DDAH-1 could lead to important new treatments. “It could help us to establish if genetic variation predisposes certain people to these diseases, or whether environmental factors exert some of their effects through modulation of DDAH activity. “Our research also shows that this pathway could be harnessed therapeutically to limit production of NO in certain situations where too much nitric oxide is a bad thing; for example, hypotension and septic shock. These are some of the biggest problems in intensive care medicine and there is a huge unmet need for drug treatments.” The study, which was carried out at UCL's Rayne Institute, was funded by grants from the British Heart Foundation, the Wellcome Trust and the Medical Research Council. Professor Jeremy Pearson, Associate Medical Director of the British Heart Foundation, said: "The unexpected finding in the 1980s that a simple gas, nitric oxide (NO), is made by cells in the blood vessel wall and is a powerful control of blood vessel relaxation led to the award of the Nobel Prize in 1998 to its discoverers. "More recently, there has been increasing evidence that impairment of NO production is likely to be an important factor in the development of heart and circulatory disease, but the mechanisms responsible are not fully understood. "This study suggests for the first time that the loss of the activity of the enzyme DDAH-1 leads to reduced NO production and may cause heart and circulatory disease. These findings are likely to be important in the search for new ways to optimise the health of our blood vessels." ### Notes for Editors 1. For more information, please contact Ruth Metcalfe in the UCL Media Relations Office on tel: +44 (0)20 7679 9739, mobile: +44 (0)7990 675 947, out of hours: +44 (0)7917 271 364, e-mail: r.metcalfe@ucl.ac.uk2. 'Disruption of methylarginine metabolism impairs vascular homeostasis' is published in the February issue of the journal Nature Medicine. Advance online publication is embargoed to 18.00 GMT (13.00 US Eastern) Sunday 4 February 2007. Journalists can obtain copies of the paper by contacting the UCL Media Relations Office.3. The study was funded by the British Heart Foundation, the Wellcome Trust and the Medical Research Council. About UCL Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender, and the first to provide systematic teaching of law, architecture and medicine. In the government's most recent Research Assessment Exercise, 59 UCL departments achieved top ratings of 5* and 5, indicating research quality of international excellence. UCL is the fourth-ranked UK university in the 2006 league table of the top 500 world universities produced by the Shanghai Jiao Tong University. UCL alumni include Mahatma Gandhi (Laws 1889, Indian political and spiritual leader); Jonathan Dimbleby (Philosophy 1969, writer and television presenter); Junichiro Koizumi (Economics 1969, Prime Minister of Japan); Lord Woolf (Laws 1954, Lord Chief Justice of England & Wales); Alexander Graham Bell (Phonetics 1860s, inventor of the telephone), and members of the band Coldplay.
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2. Receptor protein appears to be key in breakdown of kidney filtration
   12-19-2007 · EurekAlert!
   Massachusetts General Hospital researchers have identified a new molecular pathway that appears to be involved in urinary protein loss, an early-stage kidney disease thet affects 100 million people around the world, and is caused by a breakdown in the kidney's filtering structures.
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3. Study provides first evidence of neural link between sleep loss and psychiatric disorders
   10-22-2007 · EurekAlert!
   In the first neural investigation into what happens to our emotional stability when we lose sleep, researchers from UC Berkeley and Harvard Medical School have found that while a good night's rest can regulate our mood and help us cope with the next day's emotional challenges, sleep deprivation excessively boosts the part of the brain most closely connected to depression, anxiety and other psychiatric disorders.
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4. Insight into dopamine role suggests new treatment pathway for Parkinson's
   10-18-2006 · EurekAlert!
   Dopamine (DA) not only functions as a neurotransmitter, a chemical messenger between neurons by which one neuron triggers another, researchers have found. It also appears to coordinate the activity of a particular neural circuitry. In studies with mice, they found evidence that the dopamine deficiency in Parkinson's and other related movement disorders may cause loss of muscle control and paralysis due to disruption of coordinated activity in this circuit.
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5. NIH researchers discover protein that appears to regulate bone mass loss, the cause of osteoporosis
   03-05-2007 · EurekAlert!
   An estimated ten million Americans suffer from osteoporosis, and another 34 million Americans are at risk of developing the disease. The basic mechanism behind osteoporosis involves an imbalance between bone mineral formation and loss, but the detailed biological processes that lead to this imbalance are not completely understood. Now researchers at NIAID and colleagues are reporting new insights into the biology of bone loss based on a study of 14 people with a rare genetic disorder called X-linked Hyper IgM Syndrome.
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6. Emotional eaters susceptible to weight regain
   11-08-2007 · EurekAlert!
   Just in time for the start of the holiday eating season -- a new study finds that dieters who have the tendency to eat in response to external factors, such as at parties, have fewer problems with their weight loss than those who eat in response to emotions. Led by researchers at The Miriam Hospital's Weight Control & Diabetes Research Center, the study also found that emotional eating was associated with weight regain.
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7. Jefferson researchers uncover new evidence of prolactin's possible role in breast cancer
   09-28-2007 · EurekAlert!
   Scientists at the Kimmel Cancer Center at Jefferson in Philadelphia have discovered new molecular evidence of the role of the hormone prolactin in breast cancer. They have found that prolactin, a pituitary hormone that normally stimulates breast development and milk production, initiates a new "signaling pathway" that may regulate the growth and survival of breast cancer cells.
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8. Regulating the nuclear architecture of the cell
   12-10-2006 · EurekAlert!
   Researchers at the Department of Energy's Lawrence Berkeley National Laboratory have discovered two molecular pathways that regulate the organization of heterochromatin, the nucleolus, and other features of nuclear architecture that maintain genome stability in the fruit fly Drosophila melanogaster.
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9. Anesthesia choices for C-section lead to similar outcomes for mom, baby
   10-18-2006 · EurekAlert!
   A new systematic review compared regional and general anesthesia in women undergoing Caesarean section and their respective effects on mom and baby and found little significant difference in major clinical outcomes.
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10. Hearts of male and female rainbow trout are different
    04-30-2007 · EurekAlert!
    A new study expands upon previous findings that sex differences in cardiac performance and metabolism exist in fish in general, and have now been found to occur in rainbow trout in particular.
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