Sunday, September 16, 2012

Researchers Reveal Why Some Pain Drugs Become Less Effective Over Time



Newswire
Researchers at the University of Montreal’s Sainte-Justine Hospital have identified how neural cells are able to build up resistance to opioid pain drugs within hours. 

“A better understanding of these mechanisms will enable us to design drugs that avoid body resistance to these drugs and produce longer therapeutic responses, including prolonged opioid analgesia”, lead author Dr. Graciela Pineyro said.


Humans have known about the usefulness of opioids, which are often harvested from poppy plants, for centuries, but we have very little insight into how they lose their effectiveness in the hours, days and weeks following the first dose.

“Our study revealed cellular and molecular mechanisms within our bodies that enable us to develop resistance to this medication, or what scientists call drug tolerance,” she added.


The research team looked at how drug molecules would interact with molecules called “receptors” that exist in every cell in our body. 


Receptors, as the name would suggest, receive “signals” from the chemicals that they come into contact with, and the signals then cause the various cells to react in different ways. 

They sit on the cell wall, and wait for corresponding chemicals known as receptor ligands to interact with them. 

Ligands can be produced by our bodies or introduced, for example, as medication. 

“Until now, scientists have believed that ligands acted as ‘on-off’ switches for these receptors, all of them producing the same kind of effect with variations in the magnitude of the response they elicit,” Pineyro explained.

“We now know that drugs that activate the same receptor do not always produce the same kind of effects in the body, as receptors do not always recognize drugs in the same way. Receptors will configure different drugs into specific signals that will have different effects on the body.”


Once activated by a drug, receptors move from the surface of the cell to its interior, and once they have completed this ‘journey’, they can either be destroyed or return to the surface and used again through a process known as “receptor recycling.” 


By comparing two types of opioids – DPDPE and SNC-80 – the researchers found that the ligands (chemicals that enable interaction with the cell) that encouraged recycling produced less analgesic tolerance than those that didn’t. 

“We propose that the development of opioid ligands that favour recycling could be away of producing longer-acting opioid analgesics,” Pineyro said.


Pineyro is attempting to tease the “painkilling” function of opioids from the part that triggers mechanisms that enable tolerance build up. 


“My laboratory and my work are mostly structured around rational drug design, and trying to define how drugs produce their desired and non-desired effects, so as to avoid the second, Pineyro said. 

“If we can understand the chemical mechanisms by which drugs produce therapeutic and undesired side effects, we will be able to design better therapeutic agents.”




Notes:

The study “Differential association of receptor-Gβγ complexes with β-arrestin2 determines recycling bias and potential for tolerance of delta opioid receptor (DOR) agonists” was published in The Journal of Neuroscience on April 3, 2012. 


The research was funded by the Natural Sciences and Engineering Research Council of Canada and the Canadian Institutes of Health Research.

Dr. Graciela Pineyro, MD, PhD is affiliated with the Departments of Psychiatry and Pharmacology at the University of Montreal and the Sainte-Justine University Hospital Center (UHC)’ Research Center. 

The University of Montreal and the Sainte-Justine UHC’s Research Centre are officially known as Université de Montréal and Centre de recherche du Centre hospitalier universitaire Sainte-Justine, respectively.




Contact details:

Dr. Graciela Pineyro is available for interview in English, French or Spanish upon appointment. 


To make an appointment, please contact William Raillant-Clark of the University of Montreal at +1-514-343-7593 or w.raillant-clark@umontreal.ca .



Researchers Reveal Why Some Pain Drugs Become Less Effective Over Time

 Source: Universite de Montreal



 

Brain Aerobics make sense considering the discovery of brain plasticity.



My hobby is to listen to lectures from various universities that are posted on-line and listening to TED Conference speakers.



 - some people listen to recorded lectures on mobile devices (my desktop is my chosen device combined with good quality sound speakers)



- how do some sound engineers make these lectures digestible...



 Begin with Guidelines: 


- four experiences:  spatial,  corporeal, temporal  and relational... are a good starting point and can be found in this ancient article:

Van Manen, M. (1997). Researching Lived Experience: Human Science for an Action"


I call this 15 year old article "ancient" because the field is dynamic and probably sound engineers are gaining knowledge at the speed of the many changes in the Internet and digital technologies.


My interest is in listening to the lectures, not in lecturing or in making YouTube vignettes of myself giving speeches.  Sound engineering is well-beyond my 2nd year level physics course or my years of studying and being involved with financial markets.  I am merely a dilettante interested in knowledge for knowledge's sake.


Scientists like Michael Merzinich suggest giving our brain a work-out now and then to stave off dementia and other mental fogginess that arrives along with the aging process.  I know this because I read books and listen to speeches like the following.




Michael Merzenich studies neuroplasticity -- the brain's powerful ability to change itself and adapt -- and ways we might make use of that plasticity to heal injured brains and enhance the skills in healthy ones.

Why you should listen to him:

One of the foremost researchers of neuroplasticity, Michael Merzenich's work has shown that the brain retains its ability to alter itself well into adulthood -- suggesting that brains with injuries or disease might be able to recover function, even later in life. He has also explored the way the senses are mapped in regions of the brain and the way sensations teach the brain to recognize new patterns. Merzenich wants to bring the powerful plasticity of the brain into practical use through technologies and methods that harness it to improve learning. He founded Scientific Learning Corporation, which markets and distributes educational software for children based on models of brain plasticity. He is co-founder and Chief Science Officer of Posit Science, which creates "brain training" software also based on his research. Merzenich is professor emeritus of neuroscience at the University of California, San Francisco.
"Merzenich is perhaps the most recognizable figure in brain plasticity and how one develops competence through experience and learning."
Dominique M. Durand   Source:  http://www.ted.com/speakers/michael_merzenich.html 

Michael Merzenich on the Web

 LINK to Speech :  http://www.ted.com/talks/michael_merzenich_on_the_elastic_brain.html

Related Speakers

Related themes

Conferences

  • TED2004

Dietary fat and Coronary Heart Disease


By David Liu, PHD



Wednesday Aug 15, 2012 (foodconsumer.org) --

A person's risk for coronary heart disease is strongly influenced by his diet.

It has been known that a plant-based diet can completely stop the progression of the disease or even reverse the disease condition in many cases.


A review article by W.C. Willett of Department of Nutrition at Harvard School of Public Health in Boston MA suggests that dietary fats actually play a major role in the risk of coronary heart disease.


For his report published in the July 2012 issue of Journal of Internal Medicine, Dr. Willett reviewed 95 studies of all sorts including experimental studies, epidemiological studies and trials. 


He has found something that may help food consumers understand the role of each major type of dietary fat in the risk of coronary heart disease.


Trans fat, commonly known as partially hydrogenated vegetable oils should be eliminated from everyone's diet, according to the author, as  

they pose clear adverse effects on the risk of coronary heart disease.


It should be noted that beef and dairy products carry naturally occuring trans fat (about 15% of total fat), which is also detrimental.


Harvard nutritionists and epidemiologists have suggested that trans fat is involved in more than 100,000 deaths from heart disease.


Intake of saturated fat should be controlled and reduced intake of this type of fat may also moderately reduce the risk of coronary heart disease if saturated fat is replaced by a combination of polyunsaturated and monounsaturated fat.


Replacement of saturated fat with certain carbohydrates may also further reduce the risk of coronary heart disease. But it should be remembered that not all carbohydrates are good. Replacing saturated fat with added sugar such as cane sugar or high fructose corn syrup may not help.


Dr. Willett says in his report "both N-6 and N-3 polyunsaturated fatty acids are essential and reduce risk of heart disease, the ratio of N-6 to N-3 is not useful and can be misleading." 

This does not mean that omega-3 fatty acids are not helpful. Many nutritionists believe a low ratio of N-6 to N-3 is desirable.


Generally speaking, Americans are believed to have too high intake of omega-6 polyunsaturated fat from vegetables, which is not good for the protection against coronary heart disease.


Two undesirable oils are corn oil and soybean oil because they contain too much N-6.


In reality, the author suggests that reducing red meat and dairy products (they likely contain naturally occurring trans fat) and increasing intakes of nuts, soy foods, fish and non-hydrogenated vegetable oils can improve the fatty acid profile and help protect against coronary heart disease.


Additionally, "a diet generous in fruits, vegetables and whole grains and low in refined starches, sugar-sweetened beverages, potatoes and salt " helps prevent coronary heart disease. 


This diet is similar to the plant-based diet Dr. T. Colin Campbell, a Cornell University nutrition professor suggests.


Dr. Dean Ornish, a professor of University of California in San Fransisco in California used a plant-based diet and a lifestyle program to treat coronary heart disease patients. 


The efficacy is up to 99% and the treatment can stop effectively progression of the disease and in many cases reverse the condition.


President Bill Clinton is now using a plant-based diet (still using some fish) as advised by Dr. Ornish, and he claims that he feels much better now than ever.



Coronary heart disease kills about 600,000 Americans each year, according to the Centers for Disease Control and Prevention.



foodconsumer.org - Dietary fat and coronary heart disease


Link: http://www.foodconsumer.org/newsite/Nutrition/Diet/dietary_fat_and_coronary_heart_disease_0815120714.html

Blogger: My Fawlty Wiring


Thursday, September 13, 2012

Albert Einstein on Giving Back


Now learn how to get smarter

A hundred times every day I remind myself that my inner and outer life are based on the labors of other men, living and dead, and that I must exert myself in order to give in the same measure as I have received and am still receiving...




GET A LIFE NOW


Symptoms of Living




Tuesday, September 4, 2012

Video: Brown fat measured by thermal imaging - Telegraph












Brown fat measured by thermal imaging

Heat-seeking cameras could be used to measure people's "good fat" and determine which foods they ought to be avoiding, scientists claim. 

Brown fat is good for our bodies because it burns calories by producing large amounts of heat, which could help us avoid storing surplus energy as white fat around our waistlines.
Although it had long been known that newborn babies used brown fat to keep them warm, scientists only recently discovered that we retain small deposits of it even in adulthood.
Now researchers from Nottingham University suggest that by measuring someone's levels of brown fat, and most importantly how hot it is, they could determine which foods will help them lose or gain weight.
In a new study in the Journal of Pediatrics, Prof Michael Symonds and Dr Helen Budge demonstrated that thermal imaging cameras can be used to accurately trace people's brown fat deposits.
Because brown fat produces 300 times more heat than any other tissue type, heat-sensitive technology cannot only identify it but measure how active it is, or how much heat it is producing.
The thermal imaging technique avoids the potentially harmful radiation which has been used in previous studies to measure brown fat in adults, and which has prevented scientists accurately measuring brown fat in children for safety reasons.

By using the new technique on children as well as adults, the researchers demonstrated that children have larger stores of brown fat and produce heat much more rapidly than adults.
Dr Budge said: "Brown fat does appear to be present in higher amounts in larger people than in people of lower body weight, but we think the key difference is in how active it is from person to person.

"The reason this is exciting is that if you "switch on" brown fat and it uses up energy, then potentially that is one way of controlling body weight."

Further studies of how brown fat responds to different food groups could enable food manufacturers to include a new category of health advice on food packaging, the researchers added.

Prof Symonds said: “Potentially we could add a thermogenic index to food labels to show whether that product would increase or decrease heat production within brown fat. In other words whether it would speed up or slow down the amount of calories we burn.”




Link:  http://www.telegraph.co.uk/health/healthnews/9409635/Brown-fat-measured-by-thermal-imaging.html

Video: Brown fat measured by thermal imaging - Telegraph