Rongoa Maori: Ancient medicine with modern health benefits

The South Pacific nation of New Zealand is the ancestral home of the Maori, sea-faring settlers from the eastern Polynesia. With its unique flora and fauna, New Zealand offers a large array of plants found only in that region, many of which became part of the Maori traditional system of medicine known as Rongoa Maori.  This system is a holistic approach to body, mind, spirit and tapu – or natural law. According to the principles of Rongoa Maori, true healing puts the body, mind and spirit into harmony, according to the immutable principles of natural law.
Arriving in large canoes in 1250, the Maori settled and flourished in New Zealand, known to the Maori as Aotearoa. As they became familiar with that environment, the Maori learned about the various plants on that country’s two large islands and figured out how to employ those plants for a broad variety of health purposes. When Europeans first arrived in Aotearoa in 1624, they began an all too common practice – driving the Maori out of their homelands, appropriating vast areas of Maori tribal land, and marginalizing the indigenous Polynesians.
New Zealand, a name given by the British, remains the home of the Maori, whose culture has been badly battered by the settlers who today make up most of New Zealand’s population. Yet Maori tribal tattooing, weaving, art and dance remain important parts of New Zealand culture, and so does Rongoa Maori. Today, one of the bastions of Rongoa Maori preservation is the 64 hectare Auckland Botanic Gardens in Manurewa, South Auckland. There, director Jack Hobbs and his team are preserving and protecting plants whose roots run deep in Rongoa Maori.
The Auckland Botanic Gardens offers a spectacular array of edible plants, beautiful perennial flowers, threatened native species, palms, and a wide range of botanicals whose leaves, flowers, stems, barks, seeds and roots are part of the rich Rongoa Maori tradition. The various areas of the garden provide suitable homes to plants of varying types, from field plants to those that flourish in woods.
The Maori used flax extensively for fiber, and the Auckland Botanic Gardens features a large selection of the plants, whose blade-shaped leaves yield fiber for cordage, clothing, and weaving of all types. Experts at the gardens show visitors how to strip the long blades of the flax plant, to twist the long natural fibers, and to make slender cordage of great strength. Though the New Zealand flax fiber industry has crashed, the plants are common ornamentals, most commonly used to line roadways.
But it is the well-preserved natural pharmacy of Rongoa Maori that is one of the Gardens’ key attractions. For researchers, having so many beneficial native plants available in one location makes the Auckland Botanic Gardens a treasury of traditional healing. One of the plants featured there is Manuka (Leptospermum scoparium), a shrub whose small leaves yield an essential oil that is widely used to heal cuts, infections, burns, scrapes, sores and topical problems of all kinds. Anti-inflammatory and antimicrobial, Manuka has been intensively studied by scientists for its first aid applications, for which it is highly effective.
The Auckland Botanic Gardens is home to several totara trees (Podocarpus totara), which yield the extremely valuable compound totorol, a much sought-after agent used in cosmetics. The same compound also keeps the wood of totara from rotting, which has made that a highly desirable wood for building, resulting in devastation of that species.
The yellow-blossomed Kumarahou (Pomaderris kumeraho) has long been used by the Maori as a blood purifier and liver tonic – and to treat respiratory disorders including bronchitis, cough and chest congestion. The fresh leaves of the small shrub are applied to wounds, while the respiratory remedy is made by boiling the leaves in water.
The small shrub Horopito (Pseudowintera colorata) demonstrates greater ability to kill Candida albicans yeast infections than Amphotericin B, a drug developed for the same purpose. The active compound polygodial shows great effectiveness in killing various yeasts and fungi. The leaves of horopito have a sharp, peppery taste. The Maori also chewed the leaves of the plant to relieve toothache, and they made a tea of the leaves to quell diarrhea.
Today, as beverage, food, cosmetic and nutraceutical companies are seeking more natural agents for health purposes of all kinds, the world’s treasures offer an extravaganza of benefits. With hundreds of traditional Maori medicinal plants in one place, along with staff and scientists who know the plants’ compounds and uses, The Auckland Botanic Gardens offers an opportunity for those seeking valuable botanicals to dive deeply into Rongoa Maori, to discover healing treasures from antiquity whose uses are highly relevant today.
Chris Kilham is a medicine hunter who researches natural remedies all over the world, from the Amazon to Siberia. He teaches ethnobotany at the University of Massachusetts Amherst, where he is Explorer In Residence. Chris advises herbal, cosmetic and pharmaceutical companies and is a regular guest on radio and TV programs worldwide.  His field research is largely sponsored by Naturex of Avignon, France.
Source:Fox News
 

New Study Explores How the Body Uses Vitamin B to Recognize Bacterial Infection

The mechanism by which the specialized immune cells recognize products of vitamin B synthesis, triggering the body to fight infection has been discovered by scientists. The finding opens up potential targets to improve treatments or to develop a vaccine for tuberculosis.

 The study, jointly led by the University of Melbourne and Monash University and published today in the journal Nature, has revealed for the first time that the highly abundant mucosal associated invariant T cells (MAIT cells), recognise products of vitamin B synthesis from bacteria and yeast in an early step to activating the immune system. The research revealed how by-products of bacterial vitamin synthesis, including some derived from Folic acid or vitamin B9 and Riboflavin or vitamin B2, could be captured by the immune receptor MR1 thus fine-tuning the activity of MAIT cells. Dr Lars Kjer-Nielsen from the University of Melbourne led the five year study. "Humans are unable to make vitamin B and obtain it mostly from diet. Because bacteria can synthesise vitamin B, our immune system uses this as a point of difference to recognise infection," he said. "Given the relative abundance of the MAIT cells lining mucosal and other surfaces, such as the intestine, the mouth, lungs, it is quite probable that they play a protective role in many infections from thrush to tuberculosis. "This is a significant discovery that unravels the long sought target of MAIT cells and their role in immunity to infection." Professor James McCluskey of the Department of Microbiology and Immunology at the University of Melbourne said the discovery opened up opportunities for vaccine development and other potential therapeutics. "This is a major breakthrough in which Australian researchers have beaten many strong research teams around the world, becoming the first to unlock the mystery of what drives a key component of our immune system," he said. Monash University's Professor Jamie Rossjohn said the findings had major implications for understanding the interplay between gut bacteria and the immune system. "Some vitamin by-products appear to drive immunity while others dampen it," Professor Rossjohn said. The next step is to explore whether MAIT cells might also be involved in intestinal or mucosal disorders such as inflammatory bowel disease and irritable bowel syndrome. "This discovery now cracks open a new field in immunology and we can expect many research groups to focus their attention on this system," Professor Rossjohn said. "The discovery also involved collaborators at Melbourne's Bio21 Molecular Science and Biotechnology Institute, Metabolomics Australia and the University of Queensland, reflecting the importance of collaboration between researchers to be globally competitive," Professor McCluskey said. Source-Eurekalert

 

World Arthritis Day Special:US Study on Efficacy of Ayurveda medicines in rheumatoid arthritis cure

A recent U.S. study shows efficacy of Ayurveda medicines in rheumatoid arthritis cure, the study was published in the Journal of Clinical Rheumatology in June 2011 which can be accessed through PubMed of the United States National Library of Medicine at the National Institutes of Health. Personalized Ayurvedic interventions have demonstrated clinically significant improvement in rheumatoid arthritis on a par with allopathy treatment with the added advantage of lesser side-effects, according to a study
In Ayurvedic Texts numbers of herbal formulations are prescribed for the ailment which requires proper study by adopting western parameters.   In Jammu Ayurvedic scientists claim  that they are  giving the world one of the most effective drug for arthritis based on plants, the reference of the plant can be seen in ancient books Charak and Sushruta Samhitas. The research work was reported in reputed National  and international Medical Journals. Today S.Compound has become a synonymous to Boswellia Serrata. Ayurveda scientists from Jammu Dr. Virender Mahajan told that they are awarded National as well as J&K Government Award for the research work on arthritis drug.The western Doctors stated S.Compound/Boswellia Serrata as a Leukotriene inhibitor, so they tried in Colitis, bronchitis and  even in Cancer and found positive results and  published their work. The need of hour is to provide qualitative medical service to the ailing society. He is sure that young doctors will opt for research and explore the hidden treasure of ancient science with positive approach.

Take a Look at Some of Creative Reasons for Being Absent from Work

A recent survey found that 30% of the employees resort to giving fake excuses to be absent from work. Some of the excuses were so creative that they merit a mention.One such imaginative reason - somebody actually called their boss to say that his toe got stuck in the faucet.  Some employees did not show up at work after feeling low. One employee said that she got so upset after watching ‘the hunger games’ that she couldn’t bear to get to work. Some of the employees gave other excuses like getting hit by a bird or a pet suffering a nervous breakdown.

 Source:Medindia

Just Minutes of 'Vigorous Exercise' can Lead to All-day Calorie Burn

Exercisers can burn as many as 200 extra calories in as little as 2.5 minutes of concentrated effort a day as long as they intersperse longer periods of easy recovery in a practice known as sprint interval training, researchers say. The finding could make exercise more manageable for would-be fitness buffs by cramming truly intense efforts into as little as 25 minutes.

 Kyle Sevits, Garrett Peltonen, Rebecca Scalzo, Scott Binns, Anna Klochak, Christopher Melby, and Christopher Bell, all of Colorado State University, and Edward Melanson and Tracy Swibas, both of University of Colorado Anschultz Medical Campus, compared volunteers' energy expenditures on two different days, one in which they performed a sprint interval workout on a stationary bicycle. Their results showed a marked uptick in the amount of calories the volunteers burned on the workout day, despite the short amount of time spent in actual hard exercise. Study leader Sevits notes that despite exercise's numerous documented benefits, few people hit the U.S. government's recommendations of 150 minutes of moderate exercise or 75 minutes of vigorous exercise per week. "Research shows that many people start an exercise program but just can't keep it up," Sevits said. "The biggest factor people quote is that they don't have the time to fit in exercise. We hope if exercise can be fit into a smaller period of time, then they may give exercise a go and stick with it," Sevtis said. Though other studies have shown that sprint interval training can markedly improve fitness and athletic performance, little was known about how this type of exercise affects energy expenditure, a factor that motivates many people to exercise. To determine how many calories a typical sprint interval training workout might burn, Sevits and his colleagues recruited five healthy male volunteers, all between the ages of 25 and 31 years old. These volunteers made an initial visit to Colorado State University in Fort Collins in which they performed an exercise stress test to make sure their hearts were healthy enough to participate. The researchers also analyzed the volunteers' body compositions and their resting metabolic rates. Over the next three days, the volunteers ate a diet precisely calibrated to meet their metabolic needs so that they'd be in "energy balance", Sevits explains, with just enough calories so they weren't over-or under-eating. At the end of those three days, the men then checked in to a research facility at the University of Colorado Anschultz Medical Campus that was outfitted much like a typical hospital room. However, this room was completely enclosed, with air intake and exhaust regulated and equipment installed to analyze oxygen, carbon dioxide, and water content. Based on the results of this analysis, the researchers could determine how many calories the volunteers burned while each stayed in the room. For two days, each volunteer lived in the room, continuing to eat the prescribed diet and spending the majority of their time in sedentary activities, such as watching movies or using a computer. However, on one of the days, they engaged in a sprint interval workout that involved pedalling as fast as possible on a stationary bicycle in the room that was set at a high resistance for five 30-second periods, each separated by four-minute periods of recovery in which they pedalled slowly with very little resistance. During the intense, 30-second bouts, the researchers coached the volunteers over an intercom system, encouraging them to give 100 percent effort. Analyzing results from the room calorimeter system showed that the volunteers burned an average of an extra 200 calories on the sprint interval workout day, despite spending just 2.5 minutes engaged in hard exercise. Though the researchers can't yet speculate on whether such efforts could translate into weight loss, Sevits and his colleagues suggest that engaging in intense, but brief, bursts of exercise could aid in weight maintenance. "Burning an extra 200 calories from these exercises a couple of times a week can help keep away that pound or two that many Americans gain each year," Sevits said. However, maintaining the maximum effort needed to exercise at peak intensity over the 30-second sprints could prove tricky for many people to maintain on their own without help, Sevits warns. "Motivating yourself can be very hard," he said. "The way this could work in the real world is with the guidance of a personal trainer," he added. The findings of the study will be discussed at The Integrative Biology of Exercise VI meeting being held October 10-13 at the Westin Westminster Hotel in Westminster, CO.

Source-ANI

Is moderate alcohol intake associated with risk of atrial fibrillation among patients with CVD?

An analysis of the association of alcohol consumption with the development of atrial fibrillation (AF) among subjects with coronary heart disease, stroke, diabetes, or other manifestations of cardiovascular disease (CVD) was based on subjects in two large antihypertensive drug treatment trials. Previous research in the general population has suggested an increase in the risk of the development of AF for heavy drinkers, and the present study shows such an association among subjects who already have CVD.
Among subjects in this study (all of whom had previous CVD), the authors also report that even "moderate" drinkers had a higher risk of AF than low-alcohol consumers, although the risk of death during follow up of moderate drinkers (9.9%) was lower than that of subjects reporting low-levels of drinking(12.5%). Excluding binge drinkers, the estimated risk of AF was about 13% higher in moderate drinkers than among subjects classified as low-alcohol consumers.
While the multiple analyses in this paper were done appropriately, Forum reviewers were concerned about two aspects of this study. First, there was concern about the wide range the authors chose for the category of "moderate" drinkers, which included subjects reporting from 1 drink per week up through those reporting 21 drinks per week for men and 14 drinks per week for women. It would have been useful to present results also for subjects who met more common definitions for moderate drinking: no more than 14 drinks/week for men and 7 drinks/week for women, the values used to define moderate drinking in the United States, Australia, and many other countries. Unfortunately, there is a conspicuous absence of data in this paper of the effects on the risk of AF of subjects consuming alcohol "moderately" by these standards.
Another major concern about these analyses relates to potential bias in the estimates from what is known as index event bias or collider bias. Given that alcohol intake prior to enrollment in this study may well have related to subjects' development of cardiovascular disease, it is problematic to judge the effects of alcohol after a cardiovascular event on the subsequent risk of AF, a condition frequently associated with CVD.
All subjects in these analyses had already developed CVD (the prerequisite for being in the present study). Thus, the study included those who consumed alcohol prior to the diagnosis of CVD or diabetes and those who did not drink prior to these diagnoses. Given that moderate alcohol consumption has been shown to reduce substantially the risk of both CVD and diabetes, it can be assumed that subjects in this study who developed CVD despite being drinkers had other risk factors contributing to the disease that overcame any "protection" afforded by alcohol consumption. Unless adjusted for, these other risk factors could well affect the subsequent course of subjects following the onset of CVD, including the development of AF. A similar phenomenon has been seen for obesity (the "obesity paradox"), aspirin use (the "aspirin paradox"), and other exposures, where the associations with CVD seen prior to the initial development of the disease differ from those seen after the development of CVD.
It is clear from many previous studies in the general population that heavy alcohol intake and binge drinking increase the risk of developing atrial fibrillation. This cardiac arrhythmia is a common component of the "holiday heart" syndrome that may occur after very heavy bouts of drinking. As for the effects on the risk of atrial fibrillation from moderate drinking, as studied in this paper, there were a number of concerns from Forum reviewers about the analyses and results. They raise questions about the conclusions of the authors that even "moderate" drinking results in an increased risk of atrial fibrillation after the development of cardiovascular disease. Especially when defined as no more than 14 drinks per week for men or 7 drinks per week for women, the association between "moderate" alcohol consumption and atrial fibrillation remains unclear.
Source: Boston University Medical Center

Chronic stress during pregnancy prevents brain benefits of motherhood, study shows

A new study in animals shows that chronic stress during pregnancy prevents brain benefits of motherhood, a finding that researchers suggest could increase understanding of postpartum depression.
Rat mothers showed an increase in brain cell connections in regions associated with learning, memory and mood. In contrast, the brains of mother rats that were stressed twice a day throughout pregnancy did not show this increase.
The researchers were specifically interested in dendritic spines – hair-like growths on brain cells that are used to exchange information with other neurons.
Previous animal studies conducted by lead author Benedetta Leuner of Ohio State University showed that an increase of dendritic spines in new mothers' brains was associated with improved cognitive function on a task that requires behavioral flexibility – in essence, enabling more effective multitasking. The dendritic spines increased by about 20 percent in these brain regions in new mothers, according to her findings.
The stress in this new study negated those brain benefits of motherhood, causing the stressed rats' brains to match brain characteristics of animals that had no reproductive or maternal experience.
The stressed rats also had less physical interaction with their babies than did unstressed rats, a behavior observed in human mothers who experience postpartum depression.
"Animal mothers in our research that are unstressed show an increase in the number of connections between neurons. Stressed mothers don't," said Leuner, assistant professor of psychology and neuroscience at Ohio State. "We think that makes the stressed mothers more vulnerable. They don't have the capacity for brain plasticity that the unstressed mothers do, and somehow that's contributing to their susceptibility to depression."
Leuner described the research during a talk Saturday (10/13) in New Orleans at Neuroscience 2012, the annual meeting of the Society for Neuroscience.
Previous research has suggested that there are a number of risk factors for postpartum depression, including hormone fluctuations, prior history of mental illness and environmental factors such as smoking or low socioeconomic status. One of the strongest predictors, however, is chronic stress during pregnancy, so Leuner sought to create an animal model that could help explain brain changes linked to postpartum depression.
"It's devastating not only for the mother, because it affects her well-being, but previous research also has shown that children of depressed mothers have impaired cognitive and social development, may have impaired physical development, and are more likely as adults to have depression or anxiety," she said. "A better understanding of postpartum depression is important to help the mother but also to prevent some of the damaging effects that this disorder can have on the child."
The researchers exposed pregnant rats to stress twice a day by limiting their mobility on some days and on other days placing them in water. For three weeks after the rats gave birth, Leuner and colleagues monitored the rats.
The animals showed classic signs of the effects of stress, including lower than normal weight gain and enlarged adrenal glands, a sign of high stress-hormone production. The mothers stressed during pregnancy also gave birth to smaller pups.
"And they were not very good mothers," Leuner said. After separation from pups for 30 minutes, unstressed mothers would gather up their babies, put them in the nest and nurse them. Stressed mother rats left the pups scattered around, wandered around the cage and fed the babies less frequently. The stressed mother rats also exhibited more floating than unstressed rats in a water test; animals that float rather than swim are showing depressive-like symptoms.
"These findings in rats mimic some of the symptoms that are seen in women with postpartum depression," Leuner said.
An examination of the animals' brains showed that the rats exposed to chronic stress did not grow the additional dendritic spines in the hippocampus and prefrontal cortex that the unstressed mother rats did. The stressed rats' brains more closely resembled the brains of control rats that had never been mothers.
"We don't yet know what the exact trigger is for the increase in spines in motherhood, but we know that the increase goes away with stress," Leuner said.
She is continuing the work by investigating whether the beneficial effects of motherhood on cognitive functions are also blocked in mothers who are exposed to pregnancy stress as well as whether hormonal factors play a role.
Source: Ohio State University

Department of Ayush's 'Arogya 2012' inaugurated in Hyderabad

The 'Arogya 2012', the Department of Ayush's fair to showcase the strength of Ayush systems and inevitable linkages with the industry, was inaugurated  at Hyderabad in Andhra Pradesh today by Ghulam Nabi Azad, Union Minister of Health and Family Welfare.
The four-day event is being organised in collaboration with FICCI from October 12 to 15, 2012. “Arogya” is an exhibition showcasing the strength, efficacy and affordability of the Ayush systems of medicine which include Ayurveda, Yoga & Naturopathy, Unani, Siddha, Sowa-Rigpa and Homoeopathy. The fair showcases the best and latest developments in the field of Ayush. The last Arogya fair at Hyderabad was held in November 2005.
Addressing the meeting of Arogya fair at Hyderabad, Azad, said the fair has grown into a country-wide phenomenon with more than 10 fairs organized throughout the year now. The Department of Ayush organises and supports these fairs to encourage the dissemination of information on the benefits and achievements of the Ayush systems of medicine and for sharing of experiences and best practices between the industry, academia and research institutions. The active participation of Ayush drug industries, medicinal plant traders, research institutions, hospitals, publishers and other stakeholders in the Arogya fairs ensures a wide spectrum of activities thus making it more informative and interesting for the general public.He said that over the past three decades there has been a tremendous resurgence of peoples’ interest in the Ayush Systems of Medicine, not only in India but also in many parts of the world, including Europe and the USA. This is mainly because of holistic approach towards preventive, promotive and positive health and multi-dimensional aspects of disease management in these traditional systems of medicine. It is a matter of pride that there are 504 Ayush educational institutions including 111 postgraduate colleges where about 27,000 students are admitted annually. India has the largest number of traditional and alternative medicine teaching institutions in the world. India has signed several MoUs for bilateral cooperation in the area of traditional medicine and setting up Ayurveda chairs and Ayush information centres in various countries, such as South Africa, Malaysia and Trinidad & Tobago.He said that Ayush has been adopted as one of the core strategies under NRHM to augment effective provisioning of healthcare services. Ayush services are being introduced at various levels, i.e. in the primary health centres, community health centres, sub-district and district hospitals across the country. The aim is to utilize the Ayush doctors in implementation of the national health programmes. A national survey report from National Health Systems Resource Centre says that the use of Ayush and local health traditions is the mainstay of healthcare in many rural areas.With mainstreaming of Ayush strategy under NRHM, the patients’ attendance in the PHCs, CHCs and District Hospitals has increased in the last three to four years. The Department of Ayush has set up a Traditional Knowledge Digital Library in collaboration with Council for Scientific and Industrial Research (CSIR). This initiative, well acknowledged by the World Intellectual Property Organisation (WIPO), is a patent compatible instrument for patent search and prevention of wrong patenting of products based on traditional knowledge. Ayush systems have a long history of use by the communities as it requires simple technological inputs for diagnosis of ailments and preparation of medicinal products. Organization of such fairs in other parts of the country will continue to promote our holistic systems for overall public good, Azad added.
Source:Pharmabiz

Fish Intake Cuts Heart Disease Risk

Eating more fish is the best way to save thousands of lives that succumbs to heart disease every year, finds a British University study. The Omega-3 fish oils are far more powerful than previously thought at warding off heart disease, the Daily Express cited the study by the University of Reading as saying.

Eating just two or three portions of fish like sardines, salmon or mackerel every week or taking an oil supplement will do the job, the study said. Earlier studies also showed that fish oils can dramatically cut the risk of death by slashing blood fat, and thereby reducing the chance of a blood clot. The latest study found that fish oils have a direct impact on muscle cells that control the elasticity of blood vessels. People who have suffered a heart attack are encouraged to eat more fish or take a fish oil capsule. The researchers introduced small amounts of fish oils to meals containing saturated fat eaten by both men and women, and found that muscle elasticity was improved four-fold in women and two-fold in men. The fish oils were so effective on women that they matched the benefits of L-arginine, an amino acid supplement taken for heart health. The study was published in The Journal of Lipid Research.
"While our study found fish oils to be particularly beneficial for women they are also effective for men. Adding oily fish to your diet can help increase the elasticity of our blood vessels which is key to lowering blood pressure," Christine Williams, who led the study, was quoted as saying by the British daily.

Source-IANS

'Western' Diet High in Saturated Fat Could Lead to Atherosclerosis

A diet high in saturated fat raises levels of endothelial lipase (EL), an enzyme linked with the development of atherosclerosis, researchers from Columbia University Medical Center (CUMC) revealed. Conversely their study, conducted in mice, found that a diet high in omega-3 polyunsaturated fat lowers levels of this enzyme.
The findings establish a "new" link between diet and atherosclerosis and suggest a novel way to prevent cardiovascular heart disease. In addition, the research may help to explain why the type 2 diabetes drug rosiglitazone (Avandia) has been linked to heart problems. Like other lipases, EL plays a role in the metabolism of blood lipoproteins, which are complexes of lipids (fats) and proteins. EL, which is secreted by macrophages (a type of white blood cell) and other cells in arteries, was discovered in 1999. Studies have shown that elevated EL is associated with atherosclerosis and inflammation. Until now, however, little was known about how dietary fats might affect this enzyme, said study leader Richard Deckelbaum, MD, the Robert R. Williams Professor of Nutrition professor of pediatrics and of epidemiology and director of the Institute of Human Nutrition at CUMC. In the current study, a strain of mice susceptible to atherosclerosis was fed a normal diet enriched with either palmitic acid (a common saturated fat) or eicosapentaenoic acid (an omega-3 fatty acid, or polyunsaturated fat, found in fish oil, among other foods). After 12 weeks, the mice's aortas were examined for changes in the expression of EL and inflammatory factors. Aortas of mice fed the saturated fat diet showed a significant increase in EL and detrimental changes in inflammatory factors, while those of mice fed the polyunsaturated fat diet showed a significant decrease in EL and beneficial changes in inflammatory factors. Studies in cultured macrophages showed similar results. "Our study identifies a new way in which the high-saturated-fat Western diet could lead to the development of atherosclerosis, though, of course, these results need to be confirmed in human studies," said Dr. Deckelbaum. "The findings might also explain some of the cardiovascular benefits that have been attributed to omega-3 fatty acids," he said.
The researchers also found, in cell culture studies, that macrophages fed saturated fat showed increased expression of PPAR-gamma, a cell-signalling molecule that plays a role in regulating lipid metabolism and inflammatory responses. This increase was blocked when the cells were fed an omega-3 fatty acid. "These findings are intriguing, because we know that the diabetes drug rosiglitazone (sold under the brand name Avandia) is a strong PPAR-gamma activator and that it has been associated with an increased risk of heart disease," said Dr. Deckelbaum. "So we hypothesized that if rosiglitazone activates ppar-gamma, it might also activate EL, which would explain its effects on the heart," he noted. In fact, when the macrophages were given rosiglitazone, the expression of EL increased markedly. The addition of omega-3 fatty acids to the cells blocked this increase. "This would suggest that besides raising LDL cholesterol levels, rosiglitazone can raise the risk of cardiovascular disease by increasing EL," said Dr. Deckelbaum. "In addition to its potential role in increasing arterial inflammatory responses, EL increases the anchoring of LDL to cell surfaces, which could be associated with increased LDL accumulation in coronary arteries," he added. The study was published in the online edition of Atherosclerosis, Thrombosis, and Vascular Biology.
Source-ANI

 

 

The body's own recycling system Researchers discover "molecular emergency brake" in charge of regulating self-digestion

Times of distress literally eat away at the core of starving cells: They start to digest their own parts and recycle them for metabolic purposes. This process – called autophagy – also plays a role in immune defense. In that context, however, the digestive machinery is switched on for an entirely different purpose: the elimination of pathogens that have invaded the body. Now, Prof. Ingo Schmitz at the Helmholtz Centre for Infection Research (HZI) in Braunschweig, Germany, together with a team of researchers, has discovered that a "molecular brake" is in charge of regulating autophagy to keep it from getting out of control. They published their findings in the scientific journal, Cell Death & Differentiation.
   Almost everything that happens inside a cell, including autophagy, is tightly regulated on a biochemical level. Like that, the cell makes sure that processes only take place when they are needed and that they are shut off when the need has expired. "Inside the cell, there exists a network of molecules. Between them, information is constantly being exchanged," says Schmitz, head of the research group “Systems-oriented Immunology and Inflammation Research” at HZI, who also holds a chair at the Otto von Guericke University in Magdeburg. "In a way, it looks like a big city subway map." However, only the starting point and the destination of a given "cellular subway line" are relatively easy to study. To explore the different stops along the way, is more difficult. But because other lines intersect and interact with each other at these points, it is very exciting for researchers to decode all molecules involved in these signal transduction processes. It also helps them better understand diseases caused by defects in these information highways.
 What exactly happens on a molecular level during the later stages of autophagy was largely unknown – until now. Schmitz and his team, along with researchers from the Otto von Guericke University Magdeburg, the Heinrich Heine University Düsseldorf, the Tübingen University, and the Temple University School of Medicine in Philadelphia, USA, have decoded one part of the molecular subway map. 
 Under the microscope, researchers can observe how larger-sized cellular components destined for degradation and recycling are enclosed within a small bubble, the so-called autophagosome. This structure then fuses with yet another little bubble, which digests the autophagosome's contents. "Autophagy is a survival mechanism to ensure that the cell is able to obtain the necessary nutrients during times of starvation," explains Schmitz. 
 For their studies, the scientists stained certain molecules and autophagosomes inside cells. This allowed them to observe microscopically which molecules are in charge of regulating the formation of the little digestive bubbles. To prompt self-digestion, they either starved the cells or simulated an infection. In the process, they discovered that the cells simultaneously also turned on autophagy-inhibiting molecules – "like some kind of emergency brake that ensures autophagy doesn't get out of control." Such negative feedback loops are not unusual for cells, they frequently help prevent overshooting reactions.
 The researchers managed to identify the components of this feedback loop and found a protein called p38 to play a key role in the process. The scientists were especially surprised to observe p38 proteins on the surface of the autophagosomes. Normally, this protein is localized inside the nucleus where it gets switched on whenever the cell is under stress. On the surfaces of autophagosomes, p38 performs a very different job: It alters another molecule, called Atg5, to get it to block the final step of autophagy, involving formation of the little digestive bubble. Autophagy is inhibited, and, essentially, the cell pulls the "molecular emergency brake."
 If it didn't, diseases could potentially result. As such, defective molecules of the Atg family have been implicated in the etiology of the inflammatory bowel disease, Morbus Crohn. "Looking at Atg5-deficient mice, which die of nutrient-deficiency shortly after they are born, we see just how important it is to tightly regulate autophagy," emphasizes Ralf Höcker, one of the study's first authors. As so often, it is important to find the right balance, in this case, between too much and too little self-digestion.
Source: The Helmholtz Centre for Infection Research

Curcumin curbs metastases

Powdered turmeric has been used for centuries to treat osteoarthritis and other illnesses. Its active ingredient, curcumin, inhibits inflammatory reactions. A new study now shows that it can also inhibit formation of metastases.
Prostate cancer is one of the most prevalent malignancies in the Western world, and is often diagnosed only after metastatic tumors have formed in other organs. In three percent of cases, these metastases are lethal. A research team led by PD Dr. Beatrice Bachmeier at LMU Munich has been studying the mode of action of a natural product that inhibits the formation of metastases. The compound is found in turmeric, a plant that has been used for medicinal purposes for thousands of years, and is a major ingredient of curry.
Bachmeier’s research centers on curcumin, the polyphenol responsible for the characteristic color of curry. Curcumin is well tolerated and is therefore, in principle, suitable both for prophylactic use (primary prevention) and also for the suppression of metastases in cases where an established tumor is already present (secondary prevention). In a previous study Bachmeier and her colleagues had demonstrated that the substance reduces statistically significantly the formation of lung metastases in an animal model of advanced breast cancer.
Mitigating metastasis
The new study was designed to investigate the efficacy of curcumin in the prevention of prostate cancer metastases, and to determine the agent’s mechanism of action. The researchers first examined the molecular processes that are abnormally regulated in prostate carcinoma cells. Breast and prostate cancers are often associated with latent or chronic inflammatory reactions, and in both cases, the tumor cells were found to produce pro-inflammatory immunomodulators including the cytokines CXCL1 und CXCL2.
The researchers went on to show that curcumin specifically decreases the expression of these two proteins, and in a mouse model, this effect correlated with a decline in the incidence of metastases. “Due to the action of curcumin, the tumor cells synthesize smaller amounts of cytokines that promote metastasis,” says Bachmeier. “As a consequence, the frequency of metastasis formation in the lungs is significantly reduced, in animals with breast cancer, as we showed previously, or carcinoma of the prostate, as demonstrated in our new study.”
Curcumin and chemoprevention
Bachmeier therefore believes that curcumin may be useful in the prevention of breast and prostate cancers – which are both linked to inflammation – and in reducing their metastatic potential. “This does not mean that the compound should be seen as a replacement for conventional therapies. However, it could play a positive role in primary prevention – before a full-blown tumor arises – or help to avert formation of metastases. In this context the fact that the substance is well tolerated is very important, because one can safely recommend it to individuals who have an increased tumor risk.”
A daily intake of up to 8g of curcumin is regarded as safe, and its anti-inflammatory properties have long been exploited in traditional oriental medicine. Men with benign hyperplasia of the prostate (BHP) are one possible target group for prophylaxis, as are women who have a family history of breast cancer. The agent might also be valuable as a supplement to certain cancer therapies. At all events, curcumin’s beneficial effects must first be confirmed in controlled clinical tests. Bachmeier is now planning such a trial in patients who suffer from therapy-resistant carcinoma of the prostate.
Source:LMU

Cells control energy metabolism via hedgehog signalling pathway

Cancer, diabetes, and excess body weight have one thing in common: they alter cellular metabolism. Scientists from the Max Planck Institute of Immunobiology and Epigenetics in Freiburg and the Medical University of Vienna together with an international research team have jointly resolved a new molecular circuit controlling cellular metabolism. The previously unknown signalling pathway, acting downstream of the hedgehog protein enables muscle cells and brown fat cells to absorb sugars without relying on insulin. Substances that selectively activate the signalling pathway could thus be utilized in the treatment of diabetes and obesity. With their results, the researchers are also able to explain why various new anti-cancer agents have induced mysterious pronounced side effects in the clinics.

Hedgehog was initially identified as an important protein for embryonic development across various organisms. Without hedgehog, the physiological partitions of the embryo become indistinct. However, hedgehog also influences replication, migration and specialisation of cells – that is, the processes that also play a role in carcinogenesis. Mutation of genes also occurs concomitantly in various types of cancer, such as pancreatic, gastric or intestinal carcinomas. Above and beyond this, hedgehog inhibits the formation of “bad” white adipose tissue. Brown or “good” fat that serves to control body temperature, however, remains unaffected.
Hedgehog is therefore a very promising target for medications that fight cancer, diabetes and excess body weight. The US Food and Drug Administration (FDA) approved the first hedgehog inhibitor, Vismodegib, for treatment of cancer this year. There are presently at least six further agents being tested in clinical studies. Surprisingly, the first patient cohorts receiving Vismodegib have shown serious side effects, such as weight loss and muscle cramps, to the extent that more than half of the participants in the studies had to discontinue use.
The new research results appear to explain the mysterious cramps and suggest an easy, safe and already available adjunct therapy to resolve the complication. The researchers discovered a new hedgehog signalling pathway that is independent of the activation of transcription factors and genes known thus far. Cells control their primary energy metabolism, including the glucose, fatty acid and amino acid metabolisms, via this pathway.
The membrane protein known as Smo plays an important role here. Smo controls the known signalling pathway through transcription factors, as well as the new pathway via a much faster AMP-kinase enzyme and calcium dependent pathway. Smo is activated if hedgehog binds to a specialised receptor in the cell membrane. In the signalling pathway that has now been discovered, calcium flows through the membrane channels into the cell and activates calcium-dependent enzymes that in turn activate the AMP-kinase. This completely rewires metabolism. The cell can rapidly absorb large quantities of glucose using the AMP-kinase and other enzymes, rebalancing anabolism and catabolism. Further, rather promoting efficient energy metabolism through mitochondria, the new hedgehog signalling pathway prompts much less efficient via lactic acid fermentation – a process with which cancer cells use to acquire their energy without oxygen, for example (Warburg effect).
Even more surprising, the new pathway is stimulated promiscuously by both classical activators and inhibitors of the old, “canonical” hedgehog pathway. This finding potentially flips the interpretation of tens, if not hundreds of research papers in the field. Still not clear, this could be one additional reason why hedgehog inhibitors are so effective, in essence they starve the cancer cells from the inside.
Counterintuitive inhibitor-based activation of the hedgehog and Smo-calcium/AMP-kinase signalling pathways interferes with anabolic metabolism. “Activation of the AMP-kinase and increased catabolism could explain the exaggerated weight loss of the participants in the clinical studies. More importantly though, the influx of calcium into muscle cells leads to instant contraction, and must be triggering the cramps,” explains Andrew Pospisilik from the Max Planck Institute in Freiburg. Importantly, Hedgehog inhibitors do not have to lead to these side effects. “We targeted the Smo protein with various substances and found out that there are inhibitors that do not evoke an increase in calcium or glucose values, and critically, these same inhibitors fail to cause muscle cells to contract in culture. The development of medications such as these, which have minimal side effects, is therefore entirely possible," says Pospisilik.
In addition, again using fat cells, the scientists find that cells dramatically increase the glucose quantity they can absorb – without relying on insulin. Glucose-tolerance tests on mice confirmed the findings. This was accomplished by administering a specific amount of glucose via the food and measuring the blood glucose concentration afterwards. Mice that had previously been treated with the classic hedgehog inhibitor cyclopamine had correspondingly lower blood glucose than untreated animals. Apparently, cyclopamine increases the glucose absorption, but only in the brown adipose tissue and various types of muscle tissue. Thus, researchers measured an increase in body temperature of around one degree – a sign of higher activity in brown adipose tissue.
“Agents that only activate the Smo-calcium/AMP-kinase hedgehog signalling pathway are therefore candidates as medications for treating excess body weight, as well as type-1 and type-2 diabetes. Similar to the broad hedgehog inhibitors, they possess the potential to induce muscle cramps. Thanks to our findings, we now know that a new agent must first be tested on muscle cells before it is used on humans,” says Harald Esterbauer from the Medical University of Vienna.
Source:Eurekalert

Negative Effects of Excessive Internet Use

Excessive internet use may lead to depression and loneliness, say experts. Individuals' compulsive Internet use (CIU) refers to their inability to control, reduce, or stop their online behaviour, while excessive Internet use (EIU) is the degree to which an individual feels that he or she spends an excessive amount of time online or even loses track of time when using the Internet. Mazer and Andrew M. Ledbetter of Texas Christian University have explored how specific online communication attitudes-such as individuals' tendency for online self-disclosure, online social connection, and online anxiety-predicted their compulsive and excessive Internet use and, in turn, poor well-being.
Mazer and Ledbetter found that an individual's tendency for online self disclosure and online social connection led them to use the Internet in more compulsive ways. If a person has poor face-to-face communication skills that individual will likely be more attracted to the social features of online communication, which can foster CIU. Prior research suggests that socially anxious individuals perceive online communication environments as less threatening and, as a result, are more likely to seek out communication in those settings. The findings from Mazer and Ledbetter's study are not entirely consistent with this claim, which may suggest that researchers adjust their theoretical image of the compulsive user: Whereas previous research frames online communication as a safe activity for the socially anxious to escape their communication anxiety, Mazer and Ledbetter found that compulsive users also experience anxiety when communicating online. To the extent that socially anxious individuals are drawn to the Internet, such anxiety seems to stimulate compulsive, but not necessarily excessive, use. Rather, excessive users seem to have a more realistic perception of online communication as convenient but sometimes limited in communicative effectiveness by a lack of social cues often available in face-to-face interactions. In other words, according to Mazer and Ledbetter's study, individuals' anxiety motivates CIU, while efficiency seems to motivate EIU. Mazer and Ledbetter found that CIU, not EIU, led individuals' to experience poor well-being outcomes. An article describing their study has been published in Southern Communication Journal.

Source-ANI

New Form of Yoga for Babies

Yoga helps infants as young as a few days old to 12 months to improve bodily systems, says expert. A workshop organised by the Pampers Mommy and Baby Sleep Academy in Dubai ,certified baby yoga guru Odona Farska of the Flow Yoga Dubai Studio took the infants and their mothers through a series of gentle movements that are proven to benefit them physically, physiologically and psychologically. "Baby yoga helps stimulate bodily systems like the digestive and nervous systems, besides ensure sufficient physical activity for a baby. It helps the child sleep well and heal birth traumas. It is also a bonding time for the mother and child and ensures they are happier," Gulf News quoted Farska, who mastered the art of baby yoga in London, as saying.

 She said a typical baby yoga session spans 10-15 minutes for 3-6 month-olds and 20-30 minutes for 6-12-month-olds. It covers all features of classic yoga, right from the warm-up to the stretching, postures and movements so that the vital organs are stimulated, the muscles toned and the mind and body relaxed. By extension, baby yoga is said to influence interaction with the child in every aspect, be it the manner in which he or she is lifted, carried, sat down or walked around.

Source-ANI

 

Exercise could fortify immune system against future cancers

Small pilot study suggests that T cells become more responsive in exercising cancer survivors weeks after chemo ends

Researchers may soon be able to add yet another item to the list of exercise's well-documented health benefits: A preliminary study suggests that when cancer survivors exercise for several weeks after they finish chemotherapy, their immune systems remodel themselves to become more effective, potentially fending off future incidences of cancer. The finding may help explain why exercise can significantly reduce the chances of secondary cancers in survivors or reduce the chances of cancer altogether in people who have never had the disease.
Laura Bilek, Graham Sharp, and Geoffrey Thiele, all of the University of Nebraska Medical Center, and Daniel Shackelford, Colin Quinn, and Carole Schneider, all of Rocky Mountain Cancer Rehabilitation Institute, analyzed T cells in the blood of cancer survivors before and after a 12-week exercise program. They found that a significant portion of these immune cells converted from a senescent form, which isn't as effective at combating disease, to a naïve form, ready to fight cancer and infections.
Their poster presentation entitled, "Effect of Exercise on T Cells in Cancer Survivors," will be discussed at The Integrative Biology of Exercise VI meeting being held October 10-13 at the Westin Westminster Hotel in Westminster, CO. This popular meeting is a collaborative effort between the American Physiological Society, the American College of Sports Medicine and the Canadian Society for Exercise Physiology. The conference is supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, an institute of the National Institutes of Health, GlaxoSmithKline, Inc., Stealth Peptides, Inc., and Seahorse Biosciences. The full program is online at http://bit.ly/OrMFtN.
Exercise and Immunity
Study leader Laura Bilek explains that previous research had turned up a variety of positive associations between exercise and cancer—notably, that exercise can reduce the risk of getting initial incidences of several different types of cancers, can often improve prognosis in cancer patients, and can reduce the risk of recurrence and secondary cancers survivors of some types of cancers. However, the mechanism behind these phenomena has been unknown.
Since other research has suggested that exercise can remodel the immune system, making it more effective at fighting disease in general, Bilek and her colleagues decided to investigate how exercise affects the immune system of cancer patients. Working with a group of 16 cancer survivors, all but one of who recently finished chemotherapy cancer treatment, the researchers focused on T cells, a type of immune cell that attacks a variety of infectious agents as well as cancer cells. After chemotherapy, previous research had shown that the majority of T cells become senescent, with a decreased ability to fight infections and cancers. However, Bilek says, rebuilding the population of responsive (naïve) T cells is critical for regaining normal immune function and cancer-fighting ability.
The researchers first took blood samples from each of the volunteers to examine how many senescent and naïve T cells each had. Then, these study subjects were all enrolled into 12-week exercise programs at the Rocky Mountain Cancer Rehabilitation Institute. All programs were individualized for the study participants, incorporating elements of cardiovascular exercise, strength and endurance training, and exercises for flexibility, posture, and balance, with extra emphasis in areas where participants were weak.
After the 12-week program, the researchers drew a second blood sample from each volunteer and ran the same T cell analysis.
Another Reason to Work Out
Results showed that the ratio of senescent to naïve T cells changed favorably in the majority of participants, with most of the study subjects regaining greater numbers of the naïve variety.
"What we're suggesting is that with exercise, you might be getting rid of T cells that aren't helpful and making room for T cells that might be helpful," Bilek says.
She adds that this finding highlights the importance of exercise for all, including those with cancer and cancer survivors. These two populations might benefit especially from the heightened "cancer surveillance"—the ability of the immune system to seek out and destroy budding cancers—that this study suggests exercise brings, Bilek explains.
"There's a litany of positive benefits from exercise," Bilek says. "If exercise indeed strengthens the immune system and potentially improves cancer surveillance, it's one more thing we should educate patients about as a reason they should schedule regular activity throughout their day and make it a priority in their lives."
Source:American Physiological Society

Minutes of hard exercise can lead to all-day calorie burn

Sprint interval training could cut time exercising while controlling weight

Time spent in the drudgery of strenuous exercise is a well-documented turn-off for many people who want to get in better shape. In a new study, researchers show that exercisers can burn as many as 200 extra calories in as little as 2.5 minutes of concentrated effort a day—as long as they intersperse longer periods of easy recovery in a practice known as sprint interval training. The finding could make exercise more manageable for would-be fitness buffs by cramming truly intense efforts into as little as 25 minutes.
Kyle Sevits, Garrett Peltonen, Rebecca Scalzo, Scott Binns, Anna Klochak, Christopher Melby, and Christopher Bell, all of Colorado State University, and Edward Melanson and Tracy Swibas, both of University of Colorado Anschultz Medical Campus, compared volunteers' energy expenditures on two different days, one in which they performed a sprint interval workout on a stationary bicycle. Their results showed a marked uptick in the amount of calories the volunteers burned on the workout day, despite the short amount of time spent in actual hard exercise.
Their poster presentation entitled, "A Single Session of Sprint Interval Training Increases Total Daily Energy Expenditure," will be discussed at The Integrative Biology of Exercise VI meeting being held October 10-13 at the Westin Westminster Hotel in Westminster, CO. This popular meeting is a collaborative effort between the American Physiological Society, the American College of Sports Medicine and the Canadian Society for Exercise Physiology. The conference is supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, an institute of the National Institutes of Health, GlaxoSmithKline, Inc., Stealth Peptides, Inc., and Seahorse Biosciences. The full program is online at http://bit.ly/OrMFtN.
Feeling the Burn
Study leader Sevits notes that despite exercise's numerous documented benefits, few people hit the U.S. government's recommendations of 150 minutes of moderate exercise or 75 minutes of vigorous exercise per week. "Research shows that many people start an exercise program but just can't keep it up," Sevits says. "The biggest factor people quote is that they don't have the time to fit in exercise. We hope if exercise can be fit into a smaller period of time, then they may give exercise a go and stick with it."
Though other studies have shown that sprint interval training can markedly improve fitness and athletic performance, little was known about how this type of exercise affects energy expenditure, a factor that motivates many people to exercise. To determine how many calories a typical sprint interval training workout might burn, Sevits and his colleagues recruited five healthy male volunteers, all between the ages of 25 and 31 years old. These volunteers made an initial visit to Colorado State University in Fort Collins in which they performed an exercise stress test to make sure their hearts were healthy enough to participate. The researchers also analyzed the volunteers' body compositions and their resting metabolic rates.
Over the next three days, the volunteers ate a diet precisely calibrated to meet their metabolic needs so that they'd be in "energy balance," Sevits explains, with just enough calories so they weren't over- or under-eating. At the end of those three days, the men then checked in to a research facility at the University of Colorado Anschultz Medical Campus that was outfitted much like a typical hospital room. However, this room was completely enclosed, with air intake and exhaust regulated and equipment installed to analyze oxygen, carbon dioxide, and water content. Based on the results of this analysis, the researchers could determine how many calories the volunteers burned while each stayed in the room.
For two days, each volunteer lived in the room, continuing to eat the prescribed diet and spending the majority of their time in sedentary activities, such as watching movies or using a computer. However, on one of the days, they engaged in a sprint interval workout that involved pedaling as fast as possible on a stationary bicycle in the room that was set at a high resistance for five 30-second periods, each separated by four-minute periods of recovery in which they pedaled slowly with very little resistance. During the intense, 30-second bouts, the researchers coached the volunteers over an intercom system, encouraging them to give 100 percent effort.
Sprint Interval Trainer?
Analyzing results from the room calorimeter system showed that the volunteers burned an average of an extra 200 calories on the sprint interval workout day, despite spending just 2.5 minutes engaged in hard exercise. Though the researchers can't yet speculate on whether such efforts could translate into weight loss, Sevits and his colleagues suggest that engaging in intense, but brief, bursts of exercise could aid in weight maintenance. "Burning an extra 200 calories from these exercises a couple of times a week can help keep away that pound or two that many Americans gain each year," Sevits says.
However, maintaining the maximum effort needed to exercise at peak intensity over the 30-second sprints could prove tricky for many people to maintain on their own without help, Sevits warns. "Motivating yourself can be very hard," he says. "The way this could work in the real world is with the guidance of a personal trainer."
Source:American Physiological Society

Discovery reveals important clues to cancer metastasis

In recent years investigators have discovered that breast tumors are influenced by more than just the cancer cells within them. A variety of noncancerous cells, which in many cases constitute the majority of the tumor mass, form what is known as the "tumor microenvironment." This sea of noncancerous cells and the products they deposit appear to play key roles in tumor pathogenesis.

Among the key accomplices in the tumor microenvironment are mesenchymal stem cells (MSCs), a group of adult progenitor cells which have been shown to help breast cancers maneuver and spread to other parts of the body.
Now, new research sheds further light on how this is happening. Led by investigators at Beth Israel Deaconess Medical Center (BIDMC), the findings demonstrate that the lysyl oxidase (LOX) gene is spurred to production in cancer cells as a result of their contact with MSCs, and once produced, can help ensure the spread of otherwise weakly metastatic cancer cells from primary tumors to the lung and bones. Described on-line in the Proceedings of the National Academy of Sciences (PNAS), this discovery not only provides key insights into the basic biology of tumor formation, but also offers a potential new direction in the pursuit of therapies for the treatment of bone metastasis.
"We don't have a lot of therapies that can target breast cancer once it has metastasized, particularly once cancer cells have lodged in the bone," says senior author Antoine Karnoub, PhD, an investigator in the Department of Pathology at BIDMC and Assistant Professor of Pathology at Harvard Medical School. "When breast cancer cells reach the skeleton, one way in which they cause damage is by breaking down bone tissue, which results in the bone's rich matrix releasing numerous factors. These factors, in turn, feed the cancer cells, setting in motion a vicious cycle that leaves patients susceptible to fractures, pain, and further metastasis."
MSCs are non-hematopoietic progenitor cells predominantly produced in the bone marrow that generate bone, cartilage, fat, and fibrous connective tissue. They additionally support immune cell development and are recruited to inflammatory sites throughout the body to help shut down immune responses and regenerate damaged tissues, as might occur during wound healing. Several years ago, as a postdoctoral researcher at the Whitehead Institute of the Massachusetts Institute of Technology, Karnoub began exploring the idea that MSCs were migrating to tumors after mistaking the cancer sites for inflammatory lesions in need of healing.
"We discovered that once MSCs had reached the tumor sites, they were actually helping in cancer metastasis, causing primary cancer cells to spread to other sites in the body," he explains. In this new paper, Karnoub wanted to find out, in greater molecular detail, how breast cancer cells respond to the influences of MSCs in order to better understand how cancer cells cross-talk with recruited cells in the microenvironment.
His scientific team first embarked on a straightforward experiment. "We took two dishes of cells, cancer cells and MSCs, and mixed them together," explains Karnoub. After three days, they removed the cancer cells and studied them to see how they had changed.
"We found that the lysyl oxidase [LOX] gene was highly upregulated in the cancer cells," he says. "It turns out that when a cancer cell comes in contact with an MSC, it flips on this LOX gene, turning it up by a factor of about 100. So our next question was, 'What happens to the cancer cells when they encounter this boost of LOX that they themselves have produced?'"
The answer, as revealed in subsequent experiments, was that LOX was setting in motion a cell program called epithelial-to-mesenchymal transition (EMT). During EMT, cancer cells that usually clump together undergo a transformation into cells that exhibit decreased adhesion to their neighbors and go their own way. As a result, these cancerous cells are able to migrate, significantly enhancing their ability to metastasize.
"When we put these cells back into mice, they not only formed tumors that metastasized to the lung, but also to the bone," says Karnoub. "This makes you wonder whether the cancer cells in primary tumors have become so acclimated to interacting with bone-derived MSCs that they can now grow more easily in the bone once they leave the tumor."
The investigators also wanted to find out if, by going through the EMT process, cancer cells were also acquiring the phenotypes of another highly aggressive feature of malignant cancer cells, those of cancer stem cells within the cores of most tumors.
"Cancer stem cells are believed to be responsible for the resurgence of tumors following chemotherapy treatment, and an increasing body of science is focused on understanding how CSCs function and how they originate," says Karnoub. "The processes of EMT and CSC formation have been described as being closely coupled and we asked whether LOX might be regulating CSC phenotypes, just as it was regulating EMT. To our surprise, this was not the case. This tells us that pathways that were once thought to be intimately intertwined and commonly tweaked may, in fact, be separate, and now we can start to tease out the respective circuitries with a bit more clarity."
Lastly, the investigators identified the mechanism that was enabling LOX to be turned on from outside the cell, a set of molecules called hyaluronic acid (HA) and CD44. "It turns out that the MSCs provide the HA while the cancer cells provide the CD44 and they work in tandem like a lock and key to upregulate LOX expression," explains Karnoub, adding that antagonists to HA and CD44, already in extensive investigations and clinical exploration, might be of increased use from a clinical standpoint, perhaps in managing bone metastasis
"This work reveals yet another important component of the complexity of malignant progression," says Robert Weinberg, PhD, Professor of Biology and Director of the MIT Ludwig Center for Molecular Oncology at the Massachusetts Institute of Technology. "The bidirectional communication between breast cancer cells and the nearby MSCs results in the acquisition of malignant traits by cancer cells, including their spread to distant sites in the body where they seed potentially lethal metastases."
Says Karnoub, "Now that the functions of tumor promoters and tumor suppressors are being appreciated with increased clarity, it would aid greatly if we can understand how these major cancer regulators are themselves regulated by what's outside the cancer cell. In concert with designing therapies that can enter inside the cell to directly inhibit such active players, one could perhaps design a therapy that inhibits the interaction of the cancer cell with its microenvironment, thereby shutting off the desired pathways altogether."
Source:Beth Israel Deaconess Medical Center

Antibiotic resistance a growing concern with urinary tract infection

As a result of concerns about antibiotic resistance, doctors in the United States are increasingly prescribing newer, more costly and more powerful antibiotics to treat urinary tract infections, one of the most common illnesses in women.

New research at Oregon State University suggests that the more powerful medications are used more frequently than necessary, and they recommend that doctors and patients discuss the issues involved with antibiotic therapy – and only use the stronger drugs if really neeeded.
Urinary tract infections are some of the most commonly treated infections in outpatient settings, with cystitis being the most common type. Cystitis is usually caused by E. coli bacteria that reside in the gut without causing problems, but sometimes they can cause infection.
The OSU research reports that between 1998 and 2009, about 2 percent of all doctor’s office visits by adult women were for this problem, and antibiotics were prescribed 71 percent of the time.
The problem, experts say, is that overuse of the most powerful drugs, especially quinolone antibiotics, speeds the development of bacterial resistance to these drugs. Antibiotic resistance is a natural evolutionary process by which microbes adapt to the selective pressure of medications. Some survive, and pass on their resistant traits.
These issues have gained global prominence with the dangerous and life-threatening MRSA bacteria, methicillin-resistant Staphylococcus aureus, but experts say resistance is a similar concern in many other bacteria
“Many people have heard about the issues with MRSA and antibiotic resistance, but they don’t realize that some of our much more common and frequent infections raise the same concerns,” said Jessina McGregor, an OSU assistant professor of pharmacy and expert in development of drug resistance.
Since older, inexpensive and more targeted drugs can work for treating urinary tract infections, they should be considered before the more powerful ones, she said.
“This problem is getting worse, and it’s important that we not use the new and stronger drugs unless they are really needed,” McGregor said. “That’s in everyone’s best interests, both the patient and the community. So people should talk with their doctor about risks and benefits of different treatment options to find the antibiotic best suited for them, even if it is one of the older drugs.”
McGregor recently presented data at the Interscience Conference on Antimicrobial Agents and Chemotherapy, which showed that prescriptions for quinolones rose 10 percent in recent years, while other drugs that may be equally effective in treating cystitis remained unchanged.
“Because of higher levels of antibiotic resistance to older drugs in some regions, some doctors are now starting with what should be their second choice of antibiotic, not the first,” McGregor said. “We need to conserve the effectiveness of all these anti-infective medications as best we can.”
Researchers at OSU are developing tools to help physicians select the most appropriate antibiotic for each individual. Additional information such as detailed history of past medication use, knowledge of local community levels of resistance and better doctor-patient communication can help.
“Cystitis is incredibly common, but that’s part of the reason this is a concern,” McGregor said. “It’s one of the most common reasons that many women see a doctor and are prescribed an antibiotic. And any infection can be serious if we don’t have medications that can help stop it, which is why we need to preserve
the effectiveness of all our antibiotics as long as we can.”
Source:OSU

Exercise helps ease premature cardiovascular aging caused by type 2 diabetes

Incorporating regular physical activity brings diabetic adults closer to aging rate of healthy adults

One of life's certainties is that everyone ages. However, it's also certain that not everyone ages at the same rate. According to recent research being presented this week, the cardiovascular system of people with type 2 diabetes shows signs of aging significantly earlier than those without the disease. However, exercise can help to slow down this premature aging, bringing the aging of type 2 diabetes patients' cardiovascular systems closer to that of people without the disease, says researcher Amy Huebschmann of the University of Colorado School of Medicine. She will be presenting these findings she developed with colleagues Wendy Kohrt and Judith Regensteiner, both from the same institution.
An abstract of their study entitled, "Exercise Attenuates the Premature Cardiovascular Aging Effects of Type 2 Diabetes Mellitus," will be discussed at The Integrative Biology of Exercise VI meeting being held October 10-13 at the Westin Westminster Hotel in Westminster, CO. This popular meeting is a collaborative effort between the American Physiological Society, the American College of Sports Medicine and the Canadian Society for Exercise Physiology. The conference is supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, an institute of the National Institutes of Health, GlaxoSmithKline, Inc., Stealth Peptides, Inc., and Seahorse Biosciences. The full program is online at http://bit.ly/OrMFtN.
Documented Benefits
Huebschmann and her colleagues' review of current research suggests that it's inevitable that fitness gradually decreases with age, such that a healthy adult loses about 10 percent of fitness with each decade of life after age 40 or 50. However, fitness levels are about 20 percent worse in people with type 2 diabetes than in nondiabetic adults. These findings have been shown in the adolescent, middle-aged adult, and older adult populations. Diabetes appears to place a 20 percent tax on your fitness levels at each stage of life. Not only do these patients have more trouble with exercise, the researchers say, but also with activities of daily living, such as a simple stroll to the corner store. This loss of fitness increases the mortality of people with type 2 diabetes, says Huebschmann, as well as the risk of early disability.
"It means you might move into an institutionalized setting, such as an assisted living facility, much earlier," she explains.
The good news is that exercise training can decrease these premature aging effects, a result that Huebschmann and her colleagues, as well as other researchers, have shown in various studies. Findings suggest that after 12 to 20 weeks of regular exercise, fitness in type 2 diabetic people can improve by as much as 40 percent, although fitness levels did not fully normalize to levels of nondiabetic people.
"In other words, these defects are not necessarily permanent," Huebschmann says. "They can be improved, which is great news."
Helping Diabetic People Exercise
Huebschmann, whose research involves finding and overcoming barriers of physical activity for people with type 2 diabetes, notes that each piece of research she and her colleagues present gives hope that exercise training can help lower the risks of cardiovascular problems associated with this disease. However, she adds, these findings can't make people with type 2 diabetes incorporate the recommended 150 minutes per week of moderate exercise into their lives.
"People with diabetes are typically less physically active, but the majority of those patients say that their doctors told them to be active," Huebschmann says. "There's a disconnect between what patients know they should do and what they actually do."
She and her colleagues are currently working on developing interventions that get people with type 2 diabetes to reach their exercise goals, such as receiving text messages or automated reminders.
"Type 2 diabetes has a significant negative impact on health," she says, "but that impact can be improved with as simple an intervention as regular brisk walking or other physical activity that most people with diabetes can do."
Source:American Physiological Society

Scientists discover that shape matters in DNA nanoparticle therapy

Researchers from Johns Hopkins and Northwestern universities have discovered how to control the shape of nanoparticles that move DNA through the body and have shown that the shapes of these carriers may make a big difference in how well they work in treating cancer and other diseases.This study, to be published in the Oct. 12 online edition of the journal Advanced Materials, is also noteworthy because this gene therapy technique does not use a virus to carry DNA into cells. Some gene therapy efforts that rely on viruses have posed health risks.
"These nanoparticles could become a safer and more effective delivery vehicle for gene therapy, targeting genetic diseases, cancer and other illnesses that can be treated with gene medicine," said Hai-Quan Mao, an associate professor of materials science and engineering in Johns Hopkins' Whiting School of Engineering.
Mao, co-corresponding author of the Advanced Materials article, has been developing nonviral nanoparticles for gene therapy for a decade. His approach involves compressing healthy snippets of DNA within protective polymer coatings. The particles are designed to deliver their genetic payload only after they have moved through the bloodstream and entered the target cells. Within the cells, the polymer degrades and releases DNA. Using this DNA as a template, the cells can produce functional proteins that combat disease.
A major advance in this work is that Mao and his colleagues reported that they were able to "tune" these particles in three shapes, resembling rods, worms and spheres, which mimic the shapes and sizes of viral particles. "We could observe these shapes in the lab, but we did not fully understand why they assumed these shapes and how to control the process well," Mao said. These questions were important because the DNA delivery system he envisions may require specific, uniform shapes.
To solve this problem, Mao sought help about three years ago from colleagues at Northwestern. While Mao works in a traditional wet lab, the Northwestern researchers are experts in conducting similar experiments with powerful computer models.
Erik Luijten, associate professor of materials science and engineering and of applied mathematics at Northwestern's McCormick School of Engineering and Applied Science and co-corresponding author of the paper, led the computational analysis of the findings to determine why the nanoparticles formed into different shapes.
"Our computer simulations and theoretical model have provided a mechanistic understanding, identifying what is responsible for this shape change," Luijten said. "We now can predict precisely how to choose the nanoparticle components if one wants to obtain a certain shape."
The use of computer models allowed Luijten's team to mimic traditional lab experiments at a far faster pace. These molecular dynamic simulations were performed on Quest, Northwestern's high-performance computing system. The computations were so complex that some of them required 96 computer processors working simultaneously for one month.
In their paper, the researchers also wanted to show the importance of particle shapes in delivering gene therapy. Team members conducted animal tests, all using the same particle materials and the same DNA. The only difference was in the shape of the particles: rods, worms and spheres.
"The worm-shaped particles resulted in 1,600 times more gene expression in the liver cells than the other shapes," Mao said. "This means that producing nanoparticles in this particular shape could be the more efficient way to deliver gene therapy to these cells."
The particle shapes used in this research are formed by packaging the DNA with polymers and exposing them to various dilutions of an organic solvent. DNA's aversion to the solvent, with the help of the team's designed polymer, causes the nanoparticles to contract into a certain shape with a "shield" around the genetic material to protect it from being cleared by immune cells.
Source:Northwestern University

ICMR to begin research on leptospirosis to help early diagnosis & timely treatment

In order to improve the understanding of the disease to facilitate early diagnosis and timely treatment, the Indian Council of Medical Research (ICMR) will soon begin research on leptospirosis, which is emerging as a serious public health problem in India. The research will focus on Understanding risk factors and clinical spectrum and of leptospiral infections in the country; KAP studies on risk factors and using KAP as parameter of impact evaluation of intervention programmes; understanding association of infecting serovars with clinical manifestations; virulence factors in leptospira especially those causing pulmonary manifestations; efficacy of pre- and post- exposure chemoprophylaxis in endemic areas; understand the factors that lead to variable case fatality rate across the country; evaluate commercially available diagnostic kits using a pool of samples obtained from states; and copare the existing diagnostic tests to identify gold standard for diagnostic test evaluations in relation to first and second week of fever. The study will also focus on Improving upon PCR and antigen detection tests in blood during first week of fever; standardize clinical and laboratory diagnostic criteria to make data across states comparable; evaluate immuno-fluorescence as a diagnostic tool during early phase of disease and improvements in existing immunofluorescence techniques and materials; development and evaluation of serological tests, including screening tests for use with sera from domestic livestock and other animals; immunoglobulin classes of leptospiral antibodies in man and various animals; and understanding the roles of leptospiral and host factors in the pathogenesis and manifestations of leptospiral infection and their utility as biomarker for early detection. The initiative of the ICMR in this regard is of great significance as the disease, which was confined to Andaman and Nicobar Islands and a few Southern States, has shown a rapid rise in other parts of the country, including northern states. Senior ICMR officials said that several outbreaks have been reported from Tamilnadu, Kerala, Maharashtra and Gujarat during the past few years. Heavy rainfall and the resulting flashfloods often trigger outbreaks. Timely diagnosis and specific therapy can reduce severity of illness and mortality. The majority of patients are usually from a rural background. Poor hygiene, contact with animals, rat infestation of houses, and contact with stagnant dirty water are the major determinants of disease. Leptospirosis is often not suspected by physicians in patients with acute febrile illnesses reporting from supposedly “non-endemic areas,” including north India. Morbidity and mortality reduction depends on early case detection and initiation of specific therapy. But there is difficulty in clinically distinguishing leptospirosis from other infectious diseases such as dengue, malaria, viral haemorrhagic fevers and viral hepatitis making early case detection rather unrealistic unless good laboratory support is available. Hence there is an urgent need for reliable diagnostics for Leptospirosis in the country. As of now the majority of clinical cases are confirmed using serological tests. Paired sera have to be obtained since antibodies may not appear early in the disease and seroconversion may take as long as 30 days. The reference standard serological test is the MAT (microagglutination test) which allows for the detection of the infecting serogroup. The panel of antigens in MAT must reflect the prevalent serogroups in the country. Late suspicion among primary level physicians, nonavailability of appropriate rapid diagnostic tests and the resulting inappropriate therapy leads to severe complications resulting in high mortality.

Source:Pharmabiz