Natural therapy: Research

Showing posts with label Research. Show all posts

Thursday, August 15, 2013

Research Finds Ways to Reduce the Danger of Cholesterol-lowering Statin Drugs

by Thilaka Ravi on? August 07, 2013 at 5:24 PM Drug News A recent study led by Dr. Richard Kim of the Lawson Health Research Institute, in collaboration with Dr. Robert Hegele of Robarts Research Institute, and researchers from Vanderbilt University, found that commonly occurring genetic variations in a person's genes could put the person at risk for statin-associated muscle injury. Research Finds Ways to Reduce the Danger of Cholesterol-lowering Statin Drugs
Statins, a class of drugs used to lower cholesterol, are among the best selling drugs in North America and around the world. However, statin myopathy, which results in muscle pain and weakness, is a common side effect affecting up to 10 percent of statin users.

Nearly 3-million Canadians are currently taking a statin. However, according to Dr. Kim, who is a physician at London Health Sciences Centre (LHSC) and holds the Wolfe Medical Research Chair in Pharmacogenomics at Western University, little is known about the blood levels of these drugs in a real world patient population. "Currently, we do not fully understand the drug exposure necessary for optimal statin therapy, making it difficult to predict an individual's dose requirement while minimizing the risk of side effects," states Dr. Kim. In his recent study, Dr. Kim set out to quantify patient's blood levels of statins and decipher the role genes play in statin uptake and absorption.

"We found that commonly occurring genetic variations in the genes that help to clear the drugs from the body, widely referred to as drug transporters, are key predictors of patients who will likely have high statin blood levels," says Dr. Kim. "We think those patients with high levels of statins in their blood are at a much greater risk for statin-associated muscle injury."

Currently, physicians can not readily identify at risk patients using the available clinical tests. However, Dr. Kim proposes using the pharmacogenetic tests presently available, in addition to the clinical variables he and his research team have outlined in their paper, would help to better identify these patients and prevent serious side effects. "This seems to be very relevant, especially for the many elderly patients who take these medications," says Dr. Kim.

As part of their personalized medicine program, Dr. Kim plans to utilize these pharmacogenetic tests and the algorithm they have created and apply them in a hospital and region wide fashion. As well, a larger clinical trial is being planned to compare their genomics-guided approach versus standard care in terms of better outcomes, cost-effectiveness, and prevention of adverse drug reactions.

The study, "Clinical and Pharmacogenetic Predictors of Circulating Atorvastatin and Rosuvastatin Concentration in Routine Clinical Care," was published in the July issue of Circulation: Cardiovascular Genetics.

Source-Eurekalert

var xmlHttpvar imgpath,imagefunction RefreshImage(ImageId){image=document.getElementById(ImageId);//alert(ImageId);xmlHttp=GetXmlHttpObject();if (xmlHttp==null) { alert ("Your browser does not support AJAX!"); return; } var url="http://www.medindia.net/captcha/captcha.asp";url=url+"?x="+Math.random();imgpath=url;xmlHttp.onreadystatechange=stateChangedReg;xmlHttp.open("GET",url,true);xmlHttp.send(null);} function stateChangedReg(){if (xmlHttp.readyState==4){image.src = imgpath;}}function RequestCode(){xmlHttp=GetXmlHttpObject();if (xmlHttp==null) { alert ("Your browser does not support AJAX!"); return; } var url="http://www.medindia.net/captcha/reqimgvalue.asp";url=url+"?x="+Math.random();xmlHttp.onreadystatechange=stateChangedReq;xmlHttp.open("GET",url,true);xmlHttp.send(null);} function stateChangedReq(){if (xmlHttp.readyState==4){var seccode=xmlHttp.responseText;if(seccode==document.getElementById("scode").value){//alert(seccode + "same value");}else{document.getElementById("scode").value=xmlHttp.responseText;}}}function GetXmlHttpObject(){var xmlHttpNew=null;try { // Firefox, Opera 8.0+, Safari xmlHttpNew=new XMLHttpRequest(); }catch (e) { // Internet Explorer try { xmlHttpNew=new ActiveXObject("Msxml2.XMLHTTP"); } catch (e) { xmlHttpNew=new ActiveXObject("Microsoft.XMLHTTP"); } }return xmlHttpNew;}function GetXmlHttpObject(){var xmlHttp=null;try { // Firefox, Opera 8.0+, Safari xmlHttp=new XMLHttpRequest(); }catch (e) { // Internet Explorer try { xmlHttp=new ActiveXObject("Msxml2.XMLHTTP"); } catch (e) { xmlHttp=new ActiveXObject("Microsoft.XMLHTTP"); } }return xmlHttp;}

function fnsearch(){day1 = document.search.SelDay.value;month1 = document.search.SelMonth.value;year1 = document.search.SelYear.value;tmpdate=month1+"/"+day1+"/"+year1 fromdate=new Date(year1,month1-1,day1)if (!((fromdate.getDate()==day1)&&(fromdate.getMonth()+1==month1)&&(fromdate.getFullYear()==year1))){alert("Please Select a valid Date")document.search.SelDay.focus();return false;}tmpcatid=document.search.ncategoryid.value;tmpkeyword=document.search.keyword.value;document.search.action="http://www.medindia.net/news/newsday_list.asp?ddate="+tmpdate+"&ncategoryid=" +tmpcatid +"&keyword=" +tmpkeywordreturn true;}News Categories:?? Latest Health News Popular News AIDS/HIV News Alcohol & Drug Abuse News Alternative Medicine News Anti-Aging News Bird Flu News Cancer News Celebrity Health News Chikungunya News Child Health News Cholesterol News Clinical Trials News Corporate News Dengue News Dental News Diabetes News Diet & Nutrition News Drug News Education News Environmental Health General News Genetics & Stem Cells News Health Insurance News Heart Disease News Hospital News Hypertension News Indian Health News Lifestyle News Medical Gadgets Medical PDA News Medico Legal News Men?s Health News Mental Health News News on IT in Healthcare Nursing Profession News Obesity News Organ Donation News Research News Respiratory Disease News Senior Health News Sexual Health News Tropical Disease News Weight Loss Women Health News

View the original article here

Saturday, July 20, 2013

New Research Shows How Ideas are Spread in the Brain

The research has a broad range of implications, and could lead to more effective public health campaigns, more persuasive advertisements and better ways for teachers to communicate with students, the study authors said.

"Our study suggests that people are regularly attuned to how the things they're seeing will be useful and interesting, not just to themselves but to other people," the study's senior author, Matthew Lieberman, a UCLA professor of psychology and of psychiatry and biobehavioral sciences, said.

"Before this study, we didn't know what brain regions were associated with ideas that become contagious, and we didn't know what regions were associated with being an effective communicator of ideas," lead author Emily Falk, who conducted the research as a UCLA doctoral student in Lieberman's lab and is currently a faculty member at the University of Pennsylvania's Annenberg School for Communication, said.

"Now we have mapped the brain regions associated with ideas that are likely to be contagious and are associated with being a good 'idea salesperson.' In the future, we would like to be able to use these brain maps to forecast what ideas are likely to be successful and who is likely to be effective at spreading them," she said.

The study is published online in the journal Psychological Science.

Source-ANI

View the original article here

Thursday, July 18, 2013

Research Identifies Key Factors in Understanding Differences in Rates of Birth Defects

by Rukmani Krishna on? July 06, 2013 at 12:04 AM General Health News Important information for health professionals and parents about the factors which may increase the likelihood of a baby being born with a birth defect was highlighted in new research published today in The Lancet. Research Identifies Key Factors in Understanding Differences in Rates of Birth Defects
The findings, from researchers at the Universities of Bradford and Leeds, funded by the National Institute for Health Research (NIHR), confirm that the two main factors associated with an increased risk of babies being born with a birth defect are being born to an older mother or to parents who are blood relations.

In addition, the research team was also able to confirm that socio-economic status (levels of deprivation) had no effect on the relative risk of birth defects, despite two-thirds of the mothers participating in the study coming from the most deprived fifth of the British population. The data also showed that higher levels of maternal education halved the risk of having a baby with a defect across all ethnic groups.

It has been known for some time that birth defects, also known as congenital anomalies, are a major cause of infant mortality and that their incidence varies across ethnic groups in the UK. Other studies in the last 20 years have considered consanguinity (marriage to a blood relation), as a cause of birth defects, but these studies weren't able to rule out other potential risk factors, particularly the effects of deprivation.

Geneticist and lead author Dr Eamonn Sheridan, from the University of Leeds, says:"It is important to note that the vast majority of babies born to couples who are blood relatives are absolutely fine, and whilst consanguineous marriage increases the risk of birth defect from 3% to 6%, the absolute risk is still small."

The study, funded by the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for Leeds, York and Bradford, and the largest of its type ever conducted, examined detailed information collected about more than 11,300 babies involved in the Born in Bradford (BiB) project, a unique long term study which is following the health of babies who were born in the city at the Bradford Royal Infirmary between 2007 and 2011. The research team found that the overall rate of birth defects in the BiB babies was approximately 3% - nearly double the national rate.

Each year, approximately 1.7% of babies in England and Wales are born with a birth defect (for example heart or lung problems or recognised Syndromes such as Down's), which may be life-limiting. These disorders occur as a result of complex interactions between genetic and environmental factors, or because of damage done by infections such as rubella and cytomegalovirus.

While the BiB cohort includes a total of 43 different ethnicities, the largest ethnic groups were Pakistani (45%) and White British (just under 40%).

In the Pakistani subgroup, 77% of babies born with birth defects were to parents who were in consanguineous marriages. In the White British subgroup 19% of babies with an anomaly were born to mothers over the age of 34. Links between the age of mothers and the prevalence of birth defects are already well-established.

It is estimated that more than a billion people worldwide live in in communities where consanguineous marriage is commonplace.

The Bradford/Leeds study is the first that has been able to explore the potential causes of birth defects in a population where there are enough numbers in both consanguineous and non-consanguineous groups to reach reliable and statistically significant conclusions.

Professor Neil Small, co-author of the study from the University of Bradford, says: "The research is of particular importance to Bradford, because of the characteristics of its population. Half the babies born in the city's one maternity hospital have a parent whose family origins are in Pakistan. But the findings also have relevance to other areas of the UK and across the world in countries where consanguineous marriage is a cultural norm.

"In Bradford, there are initiatives that seek to raise community awareness and services such as genetic counselling and testing in place that can be accessed by couples who are married or considering marriage to a blood relative. It is not our intention to counsel couples about who they choose to marry. But we do want to ensure that couples are aware of any risks so that they can make informed choices when planning their families," says Professor Small.

Source-Eurekalert

View the original article here

Wednesday, July 17, 2013

Low Levels of Toxic Proteins Linked to Brain Diseases: Research

Scientists studying thread-like chains of protein - called amyloid fibres - have found that low levels of these proteins may cause more harm to health than high levels.

These rarely formed protein chains, which have been linked with dozens of diseases, are produced as a result of a genetic flaw or changes in body chemistry brought about by ageing.

When this happens, short fibres are formed which become sticky and attract copies of themselves, forming an endless chain. These chains spontaneously break, creating more filament ends to which more proteins attach.

In the context of neurodegenerative diseases, it is these short, broken pieces that seem to be most harmful, scientists say.

Researchers have found that when protein levels are low, lots of short protein threads are formed. But when protein levels are high, this spontaneous breakage stops and most protein filaments remain long.

Compared with harmful short protein fibres, long fibres do not appear to be damaging in the case of neurodegenerative diseases. Researchers therefore believe that high levels of the protein - which lead to these longer chains - may actually be protective.

In addition to shedding light on disease, this insight into the protein chains may help scientists develop useful biomaterials, such as cell scaffolds, which are used for tissue engineering or to make artificial silk.

Cait MacPhee, Professor of Biological Physics at the University of Edinburgh's School of Physics and Astronomy, said; "We would expect that the higher the level of toxins, the worse the disease. However, in this study we found that the lower the level of the protein, the more of these damaging short fibres we see. Understanding how these protein chains form offers us insight not only into how diseases progress, but how we can produce controlled biomaterials for tissue engineering."

Source-Eurekalert

View the original article here

Tuesday, July 16, 2013

A New Target for Antiprion Medicines Is The Ribosome: Research

by Rukmani Krishna on? July 05, 2013 at 11:56 PM Research News The key to treating neurodegenerative prion diseases such as mad cow disease and Creutzfeldt-Jakob disease may lie in the ribosome, the protein synthesis machinery of the cell reveals new research results from Uppsala University, Sweden. The results were recently published in the Journal of Biological Chemistry. A New Target for Antiprion Medicines Is The Ribosome: Research
Prion diseases are fatal neurodegenerative diseases caused by misfolding of prion proteins. Examples of prion diseases are scrapie in sheep, mad cow disease and Creutzfeldt-Jakob disease in human.

What triggers misfolding of the prion proteins to the amyloid disease form is an open question. The inadequate knowledge in the field about the factors involved in prion formation makes the discovery of effective medicines for prion diseases rather challenging.

"We have now shown that the protein folding activity of the ribosome (PFAR) is most likely involved in prion propagation and thus, can be a specific target for antiprion medicines. If we understand the mechanism fully, we will be able to find ways to stop that too.", says Suparna Sanyal, senior lecturer at the Department of Cell and Molecular Biology, Uppsala University .

The ribosome is the protein synthesis machinery of the cell. The mechanism of protein synthesis by the ribosome is well characterized, while PFAR is a rather recent discovery. PFAR is a ribosomal RNA dependent function of the large subunit of the ribosome irrespective of its source. The PFAR center closely overlaps the peptidyl transferase center although the nucleobases responsible for these two functions are not all common.

"Our results show that two prion inhibitors 6-aminophenanthridine and guanabenz acetate implement antiprion activity by binding to ribosomal RNA and inhibiting PFAR. Thus, the ribosome and more specifically PFAR is the new target for antiprion medicines. Furthermore, we have developed an in vitro PFAR assay, which can be used as a platform for screening prion inhibitors in a high-throughput fashion. This assay is much more time and cost-effective than standard prion assays", says Suparna Sanyal.

Source-Eurekalert

View the original article here

Sunday, July 14, 2013

Childhood Respiratory Infections may Up Type 1 Diabetes Risk: Research

by Rukmani Krishna on? July 04, 2013 at 1:11 PM Child Health News A new research has warned that infections in early childhood may put children at a high risk for developing type 1 diabetes mellitus. Childhood Respiratory Infections may Up Type 1 Diabetes Risk: Research
The study included 148 children at high risk for T1D with 1,245 documented infectious events during 90,750 person-days during their first three years of life.

"Our study identified respiratory infections in early childhood, especially in the first year of life, as a risk factor for the development of T1D", the authors note.

"We also found some evidence for short-term effects of infectious events on development of autoimmunity, while cumulative exposure alone seemed not to be causative," they further wrote.

According to the results, an increased hazard ratio of islet autoantibody seroconversion was associated with respiratory infections during the first six months of life and ages 6 to almost 12 months.

During the second year of life, no meaningful associations were detected for any infectious category.

A higher number of respiratory infections in the six months prior to islet autoantibody seroconversion was also associated with an increased HR.

The study has been published by JAMA Pediatrics.

Source-ANI

View the original article here

Friday, July 12, 2013

Research Says Brain Epigenome Changes from Birth to Adolescence

Today, an article published in Science in collaboration with the group of Manel Esteller, Director of Epigenetics and Cancer Biology Biomedical Research Institute (IDIBELL), ICREA researcher and Professor of Genetics at the University of Barcelona, gives us an important clue to understanding this process.

Researchers have discovered that people's frontal cortex (the part of the brain responsible for the conduct and the acquisition of new information) experiences a significant change from birth to the end of adolescence. The epigenome is transformed.

The study analyzes the epigenome of newborns, teenagers aged 16, and adults aged 25 and 50 in the United States and in Catalonia (Spain).

Epigenome

Epigenome is the set of chemical signals responsible for turning on or off genes in our DNA. The discovery published in Science shows that one of these epigenetic signals, methylation of genetic material, is progressively increased until the end of adolescence and entry into adulthood.

"The results of the study show that DNA methylation has a key role in shaping the communication spaces between neurons (synapses)", explains Esteller. "The brain is divided into white matter (glial) and gray matter (neurons) with several cell types with different functions. DNA methylation patterns distinguish genes with cell-type specific activity. Even in the gray matter, there are cell subtypes such as pyramidal neurons and GABA neurotransmitter producers that have specific subpatterns of DNA methylation."

Source-Eurekalert

View the original article here

Changes in Hyaluronan Metabolism Key in Adaptation of Keratinocytes to Radiation Injury: Research

by Rukmani Krishna on? July 05, 2013 at 10:53 PM General Health News Epidermis as the outermost layer of skin is crucial in forming a permeability barrier and protection against various environmental agents. Thus, investigating the biology of its most important cell type, the keratinocyte, is key to understanding the effects of solar ultraviolet radiation in skin, and helps design effective means of protection against excessive exposure. UV irradiation increases the expression of hyaluronan, which is an important carbohydrate of the extracellular matrix as shown previously by both cell culture and in vivo animal models. Changes in Hyaluronan Metabolism Key in Adaptation of Keratinocytes to Radiation Injury: Research
Hyaluronan is also clearly increased in tissue sections from early stage squamous cell carcinomas, one important risk factor of which is exposure to UV radiation.Hyaluronan metabolism in cells and tissues has long been a special area of interest in the research group of Professors Raija and Markku Tammi at the Institute of Biomedicine, University of Eastern Finland. One important target tissue and focus in these studies has been the skin.

In a recent paper published in The Journal of Biological Chemistry, the group demonstrated that already fairly low doses of UVB activate the accumulation and degradation of hyaluronan. This occurs in both simple monolayer cultures of keratinocytes and a stratified, three-dimensional model that mimics normal skin epidermis. As intracellular signalling pathways are activated, the hyaluronan producing enzymes (Has1-3) and hyaluronan synthesis are upregulated. Particularly, it was shown that Has1 and Has2 are regulated by the MAP kinase p38, and Has3 by the calcium-dependent protein kinase CaMKII.Since hyaluronan content and the absolute and relative quantities and activity of the hyaluronan synthases depend on the tissue context and physiological conditions, it's crucial to understand the underlying regulatory mechanisms.

In this study, the significantly upregulated hyaluronan metabolism in the keratinocytes seemed to be dependent specifically on the Has3 enzyme. Blocking its expression with a specific siRNA reversed the UVB-induced hyaluronan production nearly to the level of the control cells. The results thus strongly indicate that epidermal keratinocytes exposed to UVB specifically activate their hyaluronan synthesis by regulating the HAS-enzymes via at least two different signalling pathways. This may be one mode for the cells to adapt to radiation damage. Even though more research is warranted, the new data further our understanding about the significance of hyaluronan for keratinocyte function under environmental stress. This activation of hyaluronan metabolism after excessive UVB exposure may also prove to be a target for regulation when trying to control and understand tissue malignancy and pre-cancerous alterations.

Source-Eurekalert

View the original article here

Wednesday, July 10, 2013

Research Finds Too Many 'Healing' Cells Delays Wound Healing

"Improvement of lymphedema is important for treatment of skin ulcers," said Makoto Sugaya, M.D., Ph.D., a researcher involved in the work from the Department of Dermatology at the University of Tokyo in Tokyo, Japan. "It is not just fluid retention, but inflammatory cells and cytokines that cause delayed wound healing."

To make this discovery, scientists used two groups of mice. The first group showed severe lymphatic dysfunction. The second group was normal. Researchers administered skin wounds and found that the mice with lymphatic dysfunction showed delayed would healing as compared to the normal mice. Analysis showed that the delayed would healing in the lymphedematous skin is the result of too many mast cells and elevated IL-10 expression, both of which can now be therapeutic targets for future drug development.

"Wound healing is something most people take for granted until there's a problem," said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology. "However, wound healing is a complex process involving immune as well as non-immune cells and problems that arise can be very serious, even if it started as a minor wound. This report provides an immunological explanation for why some wound healing is delayed, and it ultimately may help set a course for therapies that accelerate wound healing."

Source-Eurekalert

View the original article here

Tuesday, June 18, 2013

Research Highlights Challenges in Surgical Management of Spine Trauma in Morbidly Obese Patients

by Kathy Jones on? May 25, 2013 at 8:07 PM General Health News The logistic, medical, and societal challenges faced in treating spine trauma in morbidly obese patients have been described by physicians at Monash University and The Alfred Hospital in Melbourne, Australia. Research Highlights Challenges in Surgical Management of Spine Trauma in Morbidly Obese Patients
Based on a case series of six patients injured in high-speed motor vehicle accidents, the authors categorize difficulties faced in the care of morbidly obese patients from on-scene immobilization and medical transport through spinal imaging, surgery, and postoperative care. Details of the six cases and a thorough discussion of challenges posed by morbid obesity and possible solutions are covered in "Challenges in the surgical management of spine trauma in the morbidly obese patient: a case series. Clinical article," by Hannah E. Rosenfeld and colleagues, published today online, ahead of print, in the Journal of Neurosurgery: Spine.

The obesity epidemic is spreading worldwide. When patients who are morbidly obese suffer spinal injury or other major trauma, they face greater risks of complications and death compared with non-obese individuals.

The patients described in this article?five women and one man, ages 18-69 years?ranged in weight from 276 pounds (125 kilograms) to 410 pounds (186 kilograms). All six patients had a body-mass index greater than 40. These particular patients were selected because of the problems posed by their large body mass before, during, and after spine sugery.

The authors describe each case separately and then break down the obstacles faced during care of these patients into separate categories, specifically

Transport and transfer. Hailing from Australia, the authors are well aware of difficulties in transporting trauma victims from rural areas to tertiary trauma hospitals. At times, air ambulances may be the optimal choice, but these helicopters and planes have limited cabin sizes and/or weight capacities that can exclude conveyance of morbidly obese patients. This necessitates travel by road, which significantly delays diagnosis and treatment, and can have a deleterious effect on outcome. The use of a cervical collar during transport may be complicated by the large circumference of the patient's neck. Alternative stabilizers, such as sandbags and head taping, may be required. Anesthesia and resuscitation. Intubation is difficult because the anatomy makes it difficult to identify internal structures. Once intubation has been achieved, the endotracheal tube may become easily dislodged. Mechanical ventilation is problematic. Because of excess subcutaneous tissue, intravenous or intra-arterial access is difficult, as is placement of a draining tube in the urinary bladder. Monitoring of blood pressure and heart function is not always accurate in these patients. Imaging. Preoperative and intraoperative imaging is more difficult in morbidly obese patients. Some patients are too large to fit comfortably in closed MRI magnets. Expansive adipose tissue results in poor x-ray penetration and unclear CT and MRI images. In attempts to obtain better images, the patient may be subjected to greater radiation doses. Surgical positioning. The researchers point out that standard operating tables may not be wide enough or strong enough to hold morbidly obese patients. Turning these patients and transferring them to another table can be challenging and potentially harmful to the staff. Positioning these patients on a spinal frame may be difficult, because they may exceed the size limits of the frame. Surgical approaches and techniques. As mentioned earlier, intraoperative imaging is not as dependable in morbidly obese patients. Localization of spinal levels is thus much more difficult. Due to the depth of subcutaneous fat in these patients, the authors state that a longer incision may be necessary and longer instruments required. Retraction can be difficult, and harvesting of bone autografts may pose technical challenges and greater risks of morbidity. Venous problems. There can be greater venous bleeding, impaired venous return of blood to the heart, and increased events of venous thromboembolism. Postoperative wound care and pulmonary care. Morbidly obese patients face a higher incidence of wound breakdown, surgical site infection, and pressure sores than patients of lower weight. They should also be monitored to ascertain if those with cervical spine injuries are at risk for aspiration. In addition to alerting other physicians about the many obstacles impeding quick and efficient health care in morbidly obese patients with spinal injuries, the authors offer commonsense suggestions for how to overcome many of the obstacles they describe. Some examples include: fashioning makeshift cervical collar extenders; increased vigilance in monitoring airways; use of open MRI units when available; clamping together two operating tables when a large table is not available; using hoist systems in the operating room and training staff in moving obese patients; selecting nonstandard surgical approaches, when appropriate, to provide adequate access to the spine while allowing morbidly obese patients to be positioned safely for the entire operation; creation of longer surgical instruments; additional use of Cell Saver, which lessens overall blood loss during surgery; adjusting the dose of prophylactic heparin; and use of adequately sized pneumatic calf compressors. The authors also suggest that new hospital guidelines and management techniques should be developed to improve overall outcomes in obese patients, as their number is on the rise.

Source-Eurekalert

View the original article here

Sunday, June 9, 2013

Drug Reverses Alzheimer's Disease Deficits in Mice: Research

by Bidita Debnath on? May 26, 2013 at 11:14 AM Research News In an Alzheimer's disease mouse model, an anti-cancer drug reverses memory deficits, University of Pittsburgh Graduate School of Public Health researchers confirm in the journal Science. Drug Reverses Alzheimer's Disease Deficits in Mice: Research
The research, funded by the National Institutes of Health's National Institute on Aging and Alzheimer's Association, reviewed previously published findings on the drug bexarotene, approved by the U.S. Food and Drug Administration for use in cutaneous T cell lymphoma. The Pitt Public Health researchers were able to verify that the drug does significantly improve cognitive deficits in mice expressing gene mutations linked to human Alzheimer's disease, but could not confirm the effect on amyloid plaques.

"We believe these findings make a solid case for continued exploration of bexarotene as a therapeutic treatment for Alzheimer's disease," said senior author Rada Koldamova, M.D., Ph.D., associate professor in Pitt Public Health's Department of Environmental and Occupational Health.

Dr. Koldamova and her colleagues were studying mice expressing human Apolipoprotein E4 (APOE4), the only established genetic risk factor for late-onset Alzheimer's disease, or APOE3, which is known not to increase the risk for Alzheimer's disease, when a Case Western Reserve University study was published last year stating that bexarotene improved memory and rapidly cleared amyloid plaques from the brains of Alzheimer's model mice expressing mouse Apolipoprotein E (APOE). Amyloid plaques consist of toxic protein fragments called amyloid beta that seem to damage neurons in the brain and are believed to cause the associated memory deficits of Alzheimer's disease and, eventually, death.

Bexarotene is a compound chemically related to vitamin A that activates Retinoic X Receptors (RXR) found everywhere in the body, including neurons and other brain cells. Once activated, the receptors bind to DNA and regulate the expression of genes that control a variety of biological processes. Increased levels of APOE are one consequence of RXR activation by bexarotene. The Pitt researchers began studying similar compounds a decade ago.

"We were already set up to repeat the Case Western Reserve University study to see if we could independently arrive at the same findings," said co-author Iliya Lefterov, M.D., Ph.D., associate professor in Pitt Public Health's Department of Environmental and Occupational Health. "While we were able to verify that the mice quickly regained their lost cognitive skills and confirmed the decrease in amyloid beta peptides in the interstitial fluid that surrounds brain cells, we did not find any evidence that the drug cleared the plaques from their brains."

The Pitt researchers postulate that the drug works through a different biological process, perhaps by reducing soluble oligomers which, like the plaques, are composed of the toxic amyloid beta protein fragments. However, the oligomers are composed of smaller amounts of amyloid beta and, unlike the plaques, are still able to "move."

"We did find a significant decrease in soluble oligomers," said Dr. Koldamova. "It is possible that the oligomers are more dangerous than the plaques in people with Alzheimer's disease. It also is possible that the improvement of cognitive skills in mice treated with bexarotene is unrelated to amyloid beta and the drug works through a completely different, unknown mechanism."

In the Pitt experiments, mice with the Alzheimer's gene mutations expressing human APOE3 or APOE4 were able to perform as well in cognitive tests as their non-Alzheimer's counterparts 10 days after beginning treatment with bexarotene. These tests included a spatial test using cues to find a hidden platform in a water maze and a long-term memory test of the mouse's ability to discriminate two familiar objects following introduction of a third, novel object.

Bexarotene treatment did not affect the weight or general behavior of the mice. The drug was equally effective in male and female mice.

Source-Eurekalert

View the original article here

Thursday, June 6, 2013

Highly Respected Research Teams Unable to Confirm High-profile Alzheimer's Study

Those results, presented online Feb. 9, 2012, suggested that the drug bexarotene (marketed as Targretin?) could rapidly reverse the buildup of beta amyloid plaques (Aβ) ? a pathological hallmark of Alzheimer's disease ? in the brains of mice. According to the authors of the 2012 report, drug treatment quickly removed most of the plaques and brought rapid reversal of the pathological, cognitive and memory deficits related to the onset of Alzheimer's.

However, the new reports from extensive and carefully controlled studies did not show any reduction in the number of plaques or total area occupied by the plaques during or after treatment. These results are described in three "technical comments" ? one of which comes from researchers at the University of Chicago, Northwestern University, Massachusetts General Hospital, Washington University in St Louis and University of Tubingen in Germany ? to be published in the May 24, 2013, issue of Science.

"The drug has no impact on plaque burden in three strains that exhibit Aβ amyloidosis," according to that group's comment. "We have failed to support earlier findings by Cramer et al that Targretin is efficacious in reducing plaque burden in transgenic mouse models of cerebral Aβ deposition."

Comment co-author Sangram Sisodia, PhD, professor of neurosciences at the University of Chicago, said he and his colleagues were curious about the initial report in 2012.

"We were surprised and excited, even stunned, when we first saw these results presented at a small conference," said Sisodia. "The mechanism of action made some sense, but the assertion that they could reduce the areas of plaque by 50 percent within three days, and by 75 percent in two weeks, seemed too good to be true."

"We all went back to our labs and tried to confirm these promising findings," Sisodia added. "We repeated the initial experiments ? a standard process in science. Combined results are really important in this field. None of us found anything like what they described in the 2012 paper."

The researchers found no effects on plaque burden in three different strains of mice that were treated with bexarotene.

The discrepancy, besides being disappointing, also raises concerns about patient safety. The Food and Drug Administration approved bexarotene in December 1999 for a very specific use: treatment of refractory cutaneous T-cell lymphoma, a type of skin cancer. Once approved, the drug became legally available by prescription for "off-label" uses as well.

"Anecdotally, we have all heard that physicians are treating their Alzheimer's patients with bexarotene, a cancer drug with severe side effects," said co-author Robert Vassar, PhD, professor of cell and molecular biology at Northwestern University Feinberg School of Medicine. "This practice should be ended immediately, given the failure of three independent research groups to replicate the plaque-lowering effects of bexarotene."

Bexarotene has never been tested as a treatment for Alzheimer's disease in humans, not even to determine the optimal dose or duration of treatment. This drug has significant side effects, including major blood-lipid abnormalities, pancreatitis, liver function test abnormalities, thyroid axis alterations, leucopenia, headaches, fatigue, weight gain, depression, nausea, vomiting, constipation and rash.

The two other technical comments came from research teams led by Kevin Felsenstein, Todd Golde, David Borchelt and colleagues at the University of Florida and by Bart DeStrooper and colleagues at the University of Leuven, Belgium.

There is no cure or effective treatment for Alzheimer's disease, which is a progressive type of dementia that occurs when nerve cells in the brain die. When Alzheimer's was first identified in 1906, it was considered a rare disorder. Today, Alzheimer's is the most common cause of dementia. An estimated 5.3 million Americans have the disease.

Source-Eurekalert

View the original article here

Wednesday, June 5, 2013

Research Links Depression to Telomere Enzyme, Aging, Chronic Disease

by Rukmani Krishna on? May 25, 2013 at 11:42 PM Mental Health News The first symptoms of major depression may be behavioral. Despite this, the common mental illness is based in biology ? and not limited to the brain. In recent years some studies have linked major, long-term depression with life-threatening chronic disease and with earlier death, even after lifestyle risk factors have been taken into account. Research Links Depression to Telomere Enzyme, Aging, Chronic Disease
Now a research team led by Owen Wolkowitz, MD, professor of psychiatry at UC San Francisco, has found that within cells of the immune system, activity of an enzyme called telomerase is greater, on average, in untreated individuals with major depression. The preliminary findings from his latest, ongoing study will be reported today at the annual meeting of the American Psychiatric Association in San Francisco.

Telomerase is an enzyme that lengthens protective end caps on the chromosomes' DNA, called telomeres. Shortened telomeres have been associated with earlier death and with chronic diseases in population studies.

The heightened telomerase activity in untreated major depression might represent the body's attempt to fight back against the progression of disease, in order to prevent biological damage in long-depressed individuals, Wolkowitz said.

The researchers made another discovery that may suggest a protective role for telomerase. Using magnetic resonance imaging (MRI), they found that, in untreated, depressed study participants, the size of the hippocampus, a brain structure that is critical for learning and memory, was associated with the amount of telomerase activity measured in the white blood cells. Such an association at a single point in time cannot be used to conclude that there is a cause-and-effect relationship with telomerase helping to protect the hippocampus, but it is plausible, Wolkowitz said.

Remarkably, the researchers also found that the enzyme's activity went up when some patients began taking an antidepressant. In fact, depressed participants with lower telomerase activity at baseline ? as well as those in whom enzyme activity increased the most with treatment ? were the most likely to become less depressed with treatment.

"Our results are consistent with the beneficial effect of telomerase when it is boosted in animal studies, where it has been associated with the growth of new nerve cells in the hippocampus and with antidepressant-like effects, evidenced by increased exploratory behavior," Wolkowitz said. Wolkowitz cautions that his new findings are preliminary due to the small size of the study and must be confirmed through further research.

The researchers also measured telomere length in the same immune cells. Only very chronically depressed individuals showed telomere shortening, Wolkowitz said.

"The longer people had been depressed, the shorter their telomeres were," he said. "Shortened telomere length has been previously demonstrated in major depression in most, but not all, studies that have examined it. The duration of depression may be a critical factor."

The 20 depressed participants enrolled in the study had been untreated for at least six weeks and had an average lifetime duration of depression of about 13 years. After baseline evaluation and laboratory measures, 16 of the depressed participants were treated with sertraline, a member of the most popular class of anti-depressants, the serotonin-selective-reuptake-inhibitors (SSRIs), and then evaluated again after eight weeks. There were 20 healthy participants who served as controls.

The ongoing study still is accepting depressed participants who are not now taking antidepressants. Wolkowitz's team also studies chronic inflammation and the biochemical phenomenon of oxidative stress, which he said have often been reported in major depression. Wolkowitz is exploring the hypothesis that inflammation and oxidative stress play a role in telomere shortening and accelerated aging in depression.

"New insights into the mechanisms of these processes may well lead to new treatments ? both pharmacological and behavioral ? that will be distinctly different from the current generation of drugs prescribed to treat depression," he said. "Additional studies might lead to simple blood tests that can measure accelerated immune-cell aging."

Source-Eurekalert

View the original article here

DM

Thursday, August 15, 2013

Saturday, July 20, 2013

Thursday, July 18, 2013

Wednesday, July 17, 2013

Tuesday, July 16, 2013

Sunday, July 14, 2013

Friday, July 12, 2013

Wednesday, July 10, 2013

Tuesday, June 18, 2013

Sunday, June 9, 2013

Thursday, June 6, 2013

Wednesday, June 5, 2013