Study Shows Cannabis Can Treat Pain From Osteoarthritis

Pain from osteoarthritis leaves many debilitated due to stiff and swollen joints. While prescriptions are readily available for osteoarthritis sufferers, they often leave patients with the choice of living between two worlds: If they take prescription pills, they may live with less physical pain yet suffer from the wide array of side effects that pharmaceuticals are equipped with. If they choose not to take prescriptions due to side effects, they will live in the chronic physical pain caused by osteoarthritis. Basically, they are forced to choose between one form of pain or another. However, this may not be the case for much longer.

According to a study conducted by researchers from the University of Nottingham UK, alongside researchers from the University of Pittsburgh and Virginia Commonwealth University in the US, a specific cannabinoid is reduced during osteoarthritis, thus resulting in heightened pain and more rapid progression of the condition. Therefore it was concluded that activating the specific cannabinoid reduced in osteoarthritis patients, known as cannabinoid 2 (CB2), not only reduces pain, but also helps maintain symptoms and inhibits the speed at which the disease progresses as well.

Researchers studied human spines of deceased individuals who lived with osteoarthritis of the knee and discovered that they had lower levels of CB2 receptors. The more progressed the disease was, the lower the CB2 receptor levels were. In response, Research UK and the National Institutes of Health funded a study in which researchers activated CB2 receptors in lab rats with osteoarthritis in an attempt to reduce pain. The diseased rats were injected with JWH-133, a non-psychoactive synthetic cannabinoid that binds with CB2 receptors to activate them, and the results were nothing short of fascinating.

Study Reveals A New Potential Method For Pain Relief From Osteoarthritis

Results showed treating osteoarthritis by increasing CB2 receptors with the use of JWH-133 injections reduced chemicals responsible for causing inflammation in osteoarthritis, reduced excitatory nerves in the spine that are stimulated by inflammation, and increased the overall amount of CB2 receptor “message” (MRNA) and protein in nerve cells of the spine. To put it simply, activating the cannabinoid receptors that are drastically reduced in osteoarthritis patients reduced inflammation, thus reducing pain and allowing the individual to lead a higher quality of life. Furthermore, since patients with late stage osteoarthritis have drastically reduced levels of CB2 receptor “message” in the spine, increasing levels of the CB2 receptor “message” might greatly reduce the severity and rate of progression of the disease.

Sources for this article include:

http://www.nursingtimes.net

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0080440

http://www.ncbi.nlm.nih.gov

Watch the Video on Medicinal Importance of Cannabis

Low-Carbohydrate Diet More Heart-Friendly Than Low-Fat Diet

An article being published in Annals of Internal Medicine indicates that low-carbohydrate diet is more effective for weight loss and reducing cardiovascular risk factors than a low-fat diet.

More than one third of American adults have at least one form of cardiovascular disease and cardiovascular disease causes one third of all deaths. Low-carbohydrate diets are a popular strategy for weight loss, but their cardiovascular effects are unknown, especially among diverse populations. 
To compare the effects of a low-carbohydrate versus a low-fat diet on body weight and cardiovascular risk factors, researchers randomly assigned 148 men and women without clinical cardiovascular disease and diabetes to follow a low-carbohydrate (less than 40g a day) or low-fat diet (less than 30 percent of daily calories from fat). All participants were classified as obese based on body mass index and just over half of the participants were black. Both the low-carbohydrate and the low-fat groups received dietary counseling at regular intervals but had no specific calorie or energy goals. 
At one year, both black and white participants on the low-carbohydrate diet had greater decreases in weight, fat mass, and other cardiovascular risk factors than those on the low-fat diet. Note: The URL will be live at 5:00 p.m. on Monday, September 1 and can be included in news stories. For a PDF, please contact Megan Hanks. To interview the lead author, please contact Keith Brannon at kbrannon@tulane.edu or 504-862-8789.2. Rise in obesity is a substantial contributor to increased prevalence of diabetes An increase in body mass index (BMI) over time is the most important factor contributing to the observed increase in diabetes prevalence since 1976, according to a study being published in Annals of Internal Medicine. 
Diabetes is one of the most common and costly chronic disorders in the United States. Researchers analyzed data from five National Health and Nutrition Examination Surveys to determine the extent to which the increase in diabetes prevalence is explained by changing distributions of race/ethnicity, age, and obesity prevalence in U.S. adults. They found that the prevalence of diabetes nearly doubled from 1976 to 1980 and also from 1999 to 2004. During both time periods, diabetes prevalence increased more in men than in women. The increase of certain risk factors, including BMI, race and ethnicity, and age, coincided with an increased incidence of diabetes, with BMI being the greatest contributor among the three covariates. The researchers suggest that public health efforts should focus on interventions that address obesity. The increased prevalence of diabetes among men could not be explained by an increased BMI in men. Researchers suggest that future research should investigate what additional factors may contribute to the faster rise in diabetes in men than in women.Note: The URL will be live at 5:00 p.m. on Monday, September 1 and can be included in news stories. For a PDF, please contact Megan Hanks. The lead author, Dr. Andy Menke, can be contacted directly at AMenke@s-3.com or 301-628-03

 Source:Annals of Internal Medicine 

Team Identifies Important Regulators of Immune Cell Response

In a collaborative study, scientists from the Florida campus of The Scripps Research Institute (TSRI) and the La Jolla Institute for Allergy and Immunology have developed a more effective method to determine how immune cells called T cells differentiate into specialized types of cells that help eradicate infected cells and assist other immune cells during infection.

The new approach, published recently by the journal Immunity, could help accelerate laboratory research and the development of potential therapeutics, including vaccines. The method may also be used to identify the genes that underlie tumor cell development.

There are approximately 40,000 genes in each of our cells, but functions for only about half of them are known. The classical approach to determine the function of individual genes is slow.

“Typically, studies to identify differentiation players are done one gene at a time,” said Associate Professor Matthew Pipkin of TSRI, who led the study with Professor Shane Crotty of the La Jolla Institute for Allergy and Immunology. “Our study describes a novel method that can ‘screen’ entire gene families to discover the functions of a large number of individual genes simultaneously, a far more efficient methodology.”

In the new study, the team examined genes that regulate the specialization of T cells into “effector” cells that eliminate pathogens during infection and “memory” cells that survive long-term to maintain guard after the first infection has been cleared, keeping the same pathogens from re-infecting the body after it has fought them off once.

In their experiments, Pipkin, Crotty and their colleagues created a mixture of T cells, identical except that the expression of a different gene was interrupted in each cell so the pool of cells represented disruption of a large set of genes. The researchers then assessed the cells’ response to lymphocytic choriomeningitis virus (LCMV). Before-and-after-infection studies revealed which cells with interrupted genes had emerged after infection; cells in which disruption of a particular gene resulted in it being lost from the mixture indicated the gene played a role in promoting the cell’s development into an antiviral T cell.

The study successfully identified two previously unknown factors that work together during T cell differentiation—Cyclin T1 and its catalytic partner Cdk9, which together form the transcription elongation factor (P-TEFb). While widely expressed throughout the body and used in a number of developmental processes, the factors were previously unknown to be important in the differentiation of both antiviral CD4 and CD8 T cells.

“One of the regulators we uncovered normally enhances effector T cell differentiation at the expense of generating memory T cells and T cells that orchestrate antibody production,” Pipkin said. “That’s one candidate that you’d want to ‘turn down’ if you wanted to create more T cells that form memory cells and promote a more effective antibody response—something that would be extremely helpful in developing a vaccine.”

The first authors of the study, “In Vivo RNA Interference Screens Identify Regulators of Antiviral CD4+ and CD8+ T Cell Differentiation,” are Runqiang Chen and Simon Bélanger of the La Jolla Institute for Allergy and Immunology. Other authors include Megan A. Frederick of TSRI; and Bin Li, Robert J. Johnston, Nengming Xiao, Yun-Cai Liu, Sonia Sharma, Bjoern Peters and Anjana Rao of the La Jolla Institute for Allergy and Immunology. See http://www.cell.com/immunity/abstract/S1074-7613(14)00272-6

This work was supported by the National Institutes of Health (RC4 AI092763, R01 AI095634, R01 CA42471, R01 072543 and U19 AI109976) and Frenchman’s Creek Women for Cancer Research.

Source:journal Immunity

Knowing how bacteria take out trash could lead to new antibiotics

Because regulated protein degradation is critical for bacterial virulence and invasion, understanding how these proteases function should help to uncover pathways that can be targeted by new antibiotics

AMHERST, Mass. – A collaborative team of scientists including biochemist Peter Chien at the University of Massachusetts Amherst has reconstructed how bacteria tightly control their growth and division, a process known as the cell cycle, by specifically destroying key proteins through regulated protein degradation.
Regulated protein degradation uses specific enzymes called energy dependent proteases to selective destroy certain targets. Because regulated protein degradation is critical for bacterial virulence and invasion, understanding how these proteases function should help to uncover pathways that can be targeted by new antibiotics.
All organisms use controlled degradation of specific proteins to alter cellular behavior in response to internal or external cues, says Chien, an assistant professor of biochemistry and molecular biology. And, a process that has to happen as reliably and stably as cell division also has to be flexible enough to allow the organism to grow and respond to its ever-changing environment. But little has been known about the molecular mechanics of how cells meet these challenges.
This work, done in collaboration with Kathleen Ryan and colleagues at the University of California, Berkeley, was supported by the NIH's National Institute for General Medical Sciences. Results appeared this week in an early online edition of Proceedings of the National Academy of Sciences.
Energy dependent proteases can be thought of as tiny molecular-level machines, says Chien. By selectively cutting and destroying key proteins at precise time points during cell division, they take charge of when, and at what rate, a cell grows and divides. They are found in all kingdoms of life, but are especially important in bacteria where they help cells overcome stressful conditions such as an attack by antibiotic treatment.
"When the environment becomes damaging, these proteases selectively target particular proteins to stop cell division so the bacteria can turn to focus instead on repair until the stress is over," Chien explains. "Understanding how bacteria use these machines at the cellular and molecular level could reveal avenues for discovery of new drugs to treat infectious diseases."
The researchers focused on the bacterium Caulobacter crescentus. The cell cycle for this bacterium is controlled by the destruction of key proteins such as the essential transcription factor known as CtrA, but until now it has been unclear how this actually worked at the molecular level. Researchers have known for more than 20 years that one of the factors important for this protein destruction is an energy dependent protease ClpXP.
But ClpXP is always present through the bacterial cell cycle, not always actively breaking down CtrA, suggesting that more complex regulation was going on. Further, more recent work showed that CtrA degradation requires changes in second messengers, small molecules that help different cell pathways communicate with each other. CtrA degradation also needs dephosphorylation of proteins known as adaptors, Chien notes.
His graduate student Kamal Joshi found that these additional proteins were needed to create a scaffold that linked the CtrA substrate to the ClpXP protease. Importantly, this scaffold had to bind the small molecule second messengers in order to hold CtrA and had to contain properly dephosphorylated adaptors in order to hold the ClpXP protease.
"By requiring both these inputs, the cell ensures that degradation of CtrA only occurs at a very specific time," Chien summarizes. "We show that three proteins work together as a multi-component adaptor to stimulate the degradation of CtrA in Caulobacter crescentus. The adaptor only functions when one of the components, CpdR, is unphosphorylated and when another component, PopA, is bound to the signaling molecule, cyclic diguanylate. All this ensures that CtrA is only broken down during a specific window in the bacterium's cell-division cycle."

Chien recently received a five-year, $1.4 million grant from NIH to further explore how bacteria deal with stress by destroying their own proteins. His future work should reveal new pathways that could be targeted to block bacterial virulence or to prevent bacteria from resisting the stresses produced by antibiotics now in use. 
Source:Proceedings of the National Academy of Sciences.

Estrogen increases cannabis sensitivity

Females more likely to see tolerance and addiction while males get the munchies

PULLMAN, Wash. - Smoking today's concentrated pot might be risky business for women, according to new research from Washington State University. The study is the first to demonstrate sex differences in the development of tolerance to THC.
Psychology professor Rebecca Craft showed that, thanks to their estrogen levels, female rats are at least 30 percent more sensitive than males to the pain-relieving qualities of THC—the key active ingredient in cannabis. Females also develop tolerance to THC more quickly. These sensitivities could increase vulnerability to negative side effects like anxiety, paranoia and addiction.
The findings were recently published in the journal Drug and Alcohol Dependence.
The research was supported by a grant from the National Institute on Drug Abuse.
Many unknowns
Craft said other researchers, like Margaret Haney at the Columbia University Medical Center, have shown that women are more susceptible to cannabis abuse and dependence than men. Haney has documented a cannabis withdrawal syndrome of irritability, sleep disruption and decreased food intake that Craft said tends to be more severe in women. Women also have a greater tendency to relapse when trying to stop using the drug.
Despite the known differences in how marijuana affects the sexes, Craft said most THC tolerance studies have been done on males.
With recent legalization of recreational marijuana in Washington and Colorado—and many more states allowing medicinal use—Craft said there is greater burden on researchers to understand the effects of cannabis and ferret out differences between males and females.
She said the "munchie effect" appears to be the only THC reaction where males show more sensitivity than females. Studies in California found that THC stimulated the appetites of male animals more than those of females.
Cannabis complex
The marijuana plant contains more than 60 compounds known as cannabinoids. THC, or tetrahydrocannabinol, is the psychoactive ingredient behind the characteristic mental high. Cannabidiol and cannabinol occur in smaller amounts but may be useful for medical purposes.
All three compounds are present in the most common species of marijuana,Cannabis sativa and C. indica, but in varying proportions.
Craft said most medical marijuana patients prefer a balance between the cannabinoids. But when it comes to recreational pot, selective breeding has resulted in THC concentrations double or triple those seen in the 1960s and 70s.
"Marijuana is very different than it was 40 years ago," she said. "It's much higher in THC and lower in cannabidiol, so a little bit goes a very long way.
"We're more likely to see negative side effects today like anxiety, confusion, panic attacks, hallucinations or extreme paranoia," she said. "And women are at higher risk."
One of the few female studies
Most clinical drug trials have been conducted on men due to their more stable hormonal profile. Despite the recommendation of the National Institutes of Health in 1993 to include more women in studies or give good reasons not to, many researchers still avoid dealing with the hormone swings inherent in a woman's biology.
But Craft has been studying drug sensitivities in females for years.
Working with rats in her laboratory, Craft said she and her team "routinely manipulate hormones and follow females across their cycles to see if their drug sensitivities change along with their hormones. And they do…very frequently." Estrogen is the culprit.
"What we're finding with THC is that you get a very clear spike in drug sensitivity right when the females are ovulating - right when their estrogen levels have peaked and are coming down," she said.
Surprise finding
In the current study, Craft and her team examined the pain relieving effects of THC in male and female rats. After 10 days of treatment, tolerance to THC was shown to be significantly greater in females than males.
Tolerance occurs when the rat "adapts" to THC so that larger doses are required to produce the same pain-relieving effects initially seen with the first dose.
Because Craft already knew that females were more sensitive to THC, she adjusted their doses to be 30 percent lower than doses for males. The females still developed more tolerance.
"This is the lowest dose anyone has ever used to induce tolerance," she said.
The team also found that a low dose of THC did not disrupt the reproductive cycle in female rats, something that has been under debate and, Craft said, needs more study.
Medical marijuana
Hoping to gain greater insights into marijuana's medical potential, Craft and her team are also studying the effects of cannabidiol, which can counter some of THC's negative side effects.
The THC and cannabidiol studies will be extended to include chronic types of pain typically seen in people who request medical marijuana—such as those with debilitating back or joint pain, cancer, Crohn's disease, multiple sclerosis, severe muscle spasms and more.
"These people have pain that lasts for months or years," Craft said. "Tolerance develops differently and sometimes you get a lot less tolerance to a drug when people are in chronic pain."

Craft uses a standard research formulation of delta-9-THC for her studies and is approved by the U.S. Drug Enforcement Administration to work with Schedule I drugs such as cannabis.

Source: journal Drug and Alcohol Dependence.

Hard Work Could be Bad for Your Health

A new study of a cooperative bird in the Kalahari Desert suggests that unequal sharing of workloads in societies could leave the most industrious individuals at higher risk of poor health and prone to accelerated ageing.

 A team of scientists at the University of Exeter studied white-browed sparrow weavers, a social species in which all group members share offspring care duties, but the dominant male and female work hardest. 

Dominants are the only birds that breed, with dominant males singing to attract a mate and dominant females producing all of the eggs and providing most of the care for nestlings. 

Both dominants also invest most in fiercely defending the group's territory.In order to assess how these unequal workloads impact the health of the birds, the researchers measured the level of antioxidant protection in 93 sparrow weavers before and then again after a long breeding season.
 Source:University of Exeter 

Study links healthy sleep duration to less sick time from work

New research suggests that sleeping 7 to 8 hours per night is associated with the lowest risk of absence from work due to sickness. The results underscore the importance of the “Sleep Well, Be Well” campaign of the National Healthy Sleep Awareness Project, a collaboration between the Centers for Disease Control and Prevention, American Academy of Sleep Medicine, Sleep Research Society and other partners.

Results show that the risk of an extended absence from work due to sickness rose sharply among those who reported sleeping less than 6 hours or more than 9 hours per night. Further analysis found that the optimal sleep duration with the lowest risk of sickness absence from work was between 7 and 8 hours per night: 7 hours, 38 minutes for women and 7 hours, 46 minutes for men. Insomnia-related symptoms, early morning awakenings, feeling more tired than others, and using sleeping pills also were consistently associated with a significant increase in workdays lost due to sickness. 

“Optimal sleep duration should be promoted, as very long and very short sleep indicate health problems and subsequent sickness absence,” said principal investigator Tea Lallukka, PhD, specialized researcher at the Finnish Institute of Occupational Health. “Those sleeping five hours or less, or 10 hours or more, were absent from work every year for 4.6 to 8.9 days more, as compared to those with the optimal sleep length.”

The study results are published in the September issue of the journal Sleep.

“Insufficient sleep – due to inadequate or mistimed sleep – contributes to the risk for several of today’s public health epidemics, including cardiovascular disease, diabetes and obesity. Getting at least seven hours of nightly sleep is a key to overall health, which translates to less sick time away from work,” said American Academy of Sleep Medicine President Dr. Timothy Morgenthaler, a national spokesperson for the Healthy Sleep Project. The “Sleep Well, Be Well” campaign was launched earlier this year to increase awareness of the importance of sleep as one of the three pillars of a healthy lifestyle. 

The study involved a nationally representative survey of 3,760 men and women in Finland who had been working at any time in the prior year. Participants were 30-64 years old at baseline. Sleep characteristics were determined by questionnaire, and health measures were derived from physical examination conducted by field physicians. Data for work absences due to sickness were gathered from the Social Insurance Institution of Finland, which tracks all sickness absences lasting more than 10 days. The average follow-up period was seven years. 

A novel statistical method developed by study co-authors Tommi Härkänen, PhD, and Risto Kaikkonen, MSc, was used to predict adjusted average sickness absence days per working year. Additional statistical estimates found that the direct costs of sickness absence to the Finnish government and employers could decrease by up to 28 percent if sleep disturbances could be fully addressed.

“Insomnia symptoms should be detected early to help prevent sickness absence and deterioration in health, well-being and functioning,” said Lallukka. “Successful prevention of insomnia not only promotes health and work ability among employees, but it can also lead to notable savings in reduced sickness absence costs.”

The study was supported by the National Institute for Health and Welfare, the Academy of Finland and the Finnish Work and Environment Fund.
Source:Sleep

ICMR issues draft guidelines for diagnosis & management of Rickettsial diseases in India

The Indian Council of Medical Research (ICMR) has issued a set of draft guidelines for diagnosis & management of Rickettsial diseases which are considered some of the most covert, emerging and re-emerging diseases and are being increasingly recognized. Acute fever is the most common presenting symptom often associated with breathlessness, cough, nausea, vomiting, mylagia and headache.

Rickettsial infections are generally incapacitating and difficult to diagnose; untreated cases have fatality rates as high as 30-45% with multiple organ dysfunction, if not promptly diagnosed and appropriately treated . The vast variability and non-specific presentation of this infection have often made it difficult to diagnose clinically.

According to the draft guidelines, acute undifferentiated febrile illness of 5 days or more with or without eschar should be suspected as a case of Rickettsial infection. (If eschar is  resent, fever of less than 5 days duration should be considered as scrub typhus.) Other presenting features may be headache and rash (rash more often seen in fair persons), lymphadenopathy, multi-organ involvement like liver and kidney involvement and acute respiratory distress. The differential diagnosis of dengue, malaria, pneumonia, leptospirosis and typhoid should be kept in mind.

Rickettsial diseases have been documented in India since the 1930s with reports of scrub typhus from Kumaon region, Assam in soldiers in the second world war, scrub and murine typhus from Jabalpur area in Madhya Pradesh and of murine typhus from Kashmir. Surveillance in animals and in humans in different parts of India has documented significant levels of exposure to infections. Rickettsiosis has been clearly reported from several states in India including Himachal Pradesh, Tamil Nadu, Kerala, Maharashtra, Bihar, Karnataka, Jammu and Kashmir, Uttaranchal, Rajasthan, West Bengal and Meghalaya.

In some regions scrub typhus accounts for upto 50% of undifferentiated fever presenting to hospital.

Rickettsial infections are caused by a variety of obligate intracellular, gram- negative bacteria from the genera Rickettsia, Orientia, Ehrlichia, Neorickettsia, Neoehrlichia, and Anaplasma, belonging to the Alphaproteobacteria. Rickettsia are classically divided into the typhus group and spotted fever group (SFG), although the genus has been subdivided further based on phylogenetic analysis. Orientia spp. makes up the scrub typhus group.16 Rickettsial diseases are zoonoses where human beings are accidentally involved in a chain of transmission between trombiculid mites (chiggers), ticks or fleas and animals (most commonly rodents).

Among the major groups of rickettioses, commonly reported diseases in India are scrub typhus, murine flea-borne typhus, Indian Tick Typhus and Q fever. ICMR has invited suggestions and comments from the stakeholders.
Source:Pharmabiz

Enzyme controlling metastasis of breast cancer identified

Researchers at the University of California, San Diego School of Medicine have identified an enzyme that controls the spread of breast cancer. The findings, reported in the current issue of PNAS, offer hope for the leading cause of breast cancer mortality worldwide. An estimated 40,000 women in America will die of breast cancer in 2014, according to the American Cancer Society.
"The take-home message of the study is that we have found a way to target breast cancer metastasis through a pathway regulated by an enzyme," said lead author Xuefeng Wu, PhD, a postdoctoral researcher at UC San Diego.
The enzyme, called UBC13, was found to be present in breast cancer cells at two to three times the levels of normal healthy cells. Although the enzyme's role in regulating normal cell growth and healthy immune system function is well-documented, the study is among the first to show a link to the spread of breast cancer.
Specifically, Wu and colleagues with the UC San Diego Moores Cancer Center found that the enzyme regulates cancer cells' ability to transmit signals that stimulate cell growth and survival by regulating the activity of a protein called p38 which when "knocked down" prevents metastasis. Of clinical note, the researchers said a compound that inhibits the activation of p38 is already being tested for treatment of rheumatoid arthritis.
In their experiments, scientists took human breast cancer cell lines and used a lentivirus to silence the expression of both the UBC13 and p38 proteins. These altered cancer cells were then injected into the mammary tissues of mice. Although the primary tumors grew in these mice, their cancers did not spread.
"Primary tumors are not normally lethal," Wu said. "The real danger is cancer cells that have successfully left the primary site, escaped through the blood vessels and invaded new organs. It may be only a few cells that escape, but they are aggressive. Our study shows we may be able to block these cells and save lives."
Researchers have also defined a metastasis gene signature that can be used to evaluate clinical responses to cancer therapies that target the metastasis pathway.
Source:Proceedings of the National Academy of Sciences

‘Prepped’ by tumor cells, lymphatic cells encourage breast cancer cells to spread

HIV drug plus blood vessel growth-blockers could halt metastasis

Breast cancer cells can lay the groundwork for their own spread throughout the body by coaxing cells within lymphatic vessels to send out tumor-welcoming signals, according to a new report by Johns Hopkins scientists.
Writing in the Sept. 2 issue of Nature Communications, the researchers describe animal and cell-culture experiments that show increased levels of so-called signaling molecules released by breast cancer cells. These molecules cause lymphatic endothelial cells (LECs) in the lungs and lymph nodes to produce proteins called CCL5 and VEGF. CCL5 attracts tumor cells to the lungs and lymph nodes, and VEGF increases the number of blood vessels and makes them more porous, allowing tumor cells to metastasize and infiltrate the lungs.
In the same report, the researchers say maraviroc, a drug already approved for treating HIV infection, blocked the siren call of CCL5 in tests on animals and cells and prevented tumor spread (metastasis). Additional experiments using a combination of maraviroc and a drug that blocks the VEGF protein suggest that the treatment duo could be an effective way to prevent metastatic disease in human breast cancer patients, according to the researchers.
Because the anti-retroviral drug maraviroc has already been approved by the U.S. Food and Drug Administration and has been shown safe for long term, oral use, it could be tested in clinical trials sooner rather than later, says Aleksander Popel, Ph.D., a professor in the Department of Biomedical Engineering at the Johns Hopkins University School of Medicine and member of the Johns Hopkins Kimmel Cancer Center.
"It was surprising to find that LECs can play such an active and significant role in tumor spread." Popel noted. "Conventionally, lymphatic vessels are regarded mainly as passive conduits through which tumor cells spread from the primary tumor and eventually metastasize," he said. "However, we now know that lymphatic vessels enable metastasis, and other studies also show that they play an important role in whether or not immune cells recognize and attack cancer cells."
Popel and colleagues traced the influence of tumor signaling on LECs in cell cultures and in mice. Breast cancer cells were bathed in a nutrient-rich liquid, and, as the cancer cells grew, the investigators detected secretions of a signaling molecule called interleukin-6 (IL6) in the liquid.
Mice that were injected with the IL6-containing liquid experienced a continual rise in CCL5 levels in blood samples for several weeks. Nine of 10 tumor-bearing mice injected with the IL6-laden liquid developed metastases five weeks later. Only two of 10 mice, exposed to the liquid and given a combination of maraviroc and a VEGF-blocking drug, developed metastases.
Because maraviroc blocks the actions of CCL5, it could be delivered, along with standard chemotherapy, right after surgically removing a tumor in a bid to prevent any leftover circulating tumor cells from finding a new metastatic niche in the body, Popel says.
"However, IL6-secreting tumors could be laying the groundwork for metastasis much earlier than surgery occurs in a patient," he said. "To prevent metastatic sites from taking root, we could administer drugs that block IL6 before surgery."
The study did not address when or how to remove lymph node tissue surgically, as is often done as part of breast cancer treatment, but Popel and colleagues hope to explore the issue in future studies.
Source:Nature Communications

Study links sex hormone levels in the blood to risk of sudden cardiac arrest

For first time, researchers analyze levels of testosterone and estradiol to predict patients' likelihood of suffering usually fatal condition, take another step toward offering preventive treatments

LOS ANGELES (Sept. 2, 2014) – Measuring the levels of sex hormones in patients' blood may identify patients likely to suffer a sudden cardiac arrest, a heart rhythm disorder that is fatal in 95 percent of patients.
A new study, published online by the peer-reviewed journal Heart Rhythm, shows that lower levels of testosterone, the predominant male sex hormone, were found in men who had a sudden cardiac arrest. Higher levels of estradiol, the major female sex hormone, were strongly associated with greater chances of having a sudden cardiac arrest in both men and women.
"Because sudden cardiac arrest is usually fatal, we are constantly looking for ways to predict which patients are susceptible so we can concentrate on prevention," said Sumeet Chugh, MD, director of the Heart Rhythm Center in the Cedars-Sinai Heart Institute and the Pauline and Harold Price Chair in Cardiac Electrophysiology Research. "If we wait until someone has a sudden cardiac arrest, it is usually too late for treatment."
Unlike heart attacks (myocardial infarction), which are typically caused by clogged coronary arteries reducing blood flow to the heart muscle, sudden cardiac arrest is the result of defective electrical impulses. Patients may have little or no warning, and the disorder usually causes nearly instantaneous death. Every year, 250,000 to 300,000 people in the U.S. and up to 5 million worldwide die from sudden cardiac arrest.
Despite years of significant advances in emergency medicine and resuscitation, just 5 percent of those who suffer sudden cardiac arrest survive. For patients at known risk for this or other heart rhythm abnormalities, an implantable cardioverter-defibrillator, or ICD, may be placed in the chest or abdomen to detect faulty electrical impulses and provide a shock to return normal rhythm.
The sex hormone findings are a result of the Oregon Sudden Unexpected Death Study, a comprehensive, 16-hospital, multiyear assessment of cardiac deaths in the 1 million population Portland, Oregon metropolitan area. Led by Chugh and funded in part by the National Heart, Lung, and Blood Institute, the study's goal is to shed light on the risk factors, triggers and genetic defects associated with sudden cardiac death.
"This is the first time it has been reported that there is an association between sex hormone levels and sudden cardiac arrest," said Chugh. "While these findings need to be confirmed by other studies, they suggest that higher testosterone levels in men may offer protection from sudden cardiac arrest and lower levels of estrogen may protect both men and women."
Researchers measured blood hormone levels in 149 patients who had a sudden cardiac arrest, comparing them with levels in 149 patients who had coronary artery disease but did not have sudden cardiac arrest.
The study's findings include:

• Men who had sudden cardiac arrests had testosterone levels of 4.4 nanograms per milliliter, compared to 5.4 nanograms per milliliter for men who did not have sudden cardiac arrest.
• Men who had sudden cardiac arrest had estradiol levels of 68 picograms per milliliter, compared to 52 picograms per milliliter for men who did not have sudden cardiac arrest.
• Women who had sudden cardiac arrest had estradiol levels of 54 picograms per milliliter, compared to 36 picograms per milliliter for the control group.
• Source:journal Heart Rhythm

Sugar Substance 'Kills' Good HDL Cholesterol

University of Warwick scientists have discovered that methylglyoxal - MG substance was found to turn good HDL cholesterol into bad LDL cholesterol.

 The substance, methylglyoxal - MG, was found to damage 'good' HDL cholesterol, which removes excess levels of bad cholesterol from the body. 

Low levels of HDL, High Density Lipoprotein, are closely linked to heart disease, with increased levels of MG being common in the elderly and those with diabetes or kidney problems. 

Supported by funding from the British Heart Foundation (BHF) and published in Nutrition and Diabetes, the researchers discovered that MG destabilises HDL and causes it to lose the properties which protect against heart disease. 

HDL damaged by MG is rapidly cleared from the blood, reducing its HDL content, or remains in plasma having lost its beneficial function. 

Lead researcher Dr Naila Rabbani, of the Warwick Medical School, says that: "MG damage to HDL is a new and likely important cause of low and dysfunctional HDL, and could count for up to a 10% risk of heart disease". 

There are currently no drugs that can reverse low levels of HDL, but the Warwick researchers argue that by discovering how MG damages HDL has provided new potential strategies for reducing MG levels.

 Source:Nutrition and Diabetes

Dyslexic Readers Have Weak Network Connections in the Brain: Study

The most commonly diagnosed learning disability in US, dyslexia, is a neurological reading disability that occurs when the regions of the brain that process written language don't function normally.
 The use of non-invasive functional neuroimaging tools has helped characterize how brain activity is disrupted in dyslexia. However, most prior work has focused on only a small number of brain regions, leaving a gap in our understanding of how multiple brain regions communicate with one another through networks, called functional connectivity, in persons with dyslexia. 

This led neuroscience PhD student Emily Finn and her colleagues at the Yale University School of Medicine to conduct a whole-brain functional connectivity analysis of dyslexia using functional magnetic resonance imaging (fMRI). They report their findings in the current issue of Biological Psychiatry. 

"In this study, we compared fMRI scans from a large number of both children and young adults with dyslexia to scans of typical readers in the same age groups. Rather than activity in isolated brain regions, we looked at functional connectivity, or coordinated fluctuations between pairs of brain regions over time," explained Finn. 

In total, they recruited and scanned 75 children and 104 adults. Finn and her colleagues then compared the whole-brain connectivity profiles of the dyslexic readers to the non-impaired readers, which revealed widespread differences. 

Dyslexic readers showed decreased connectivity within the visual pathway as well as between visual and prefrontal regions, increased right-hemisphere connectivity, reduced connectivity in the visual word-form area, and persistent connectivity to anterior language regions around the inferior frontal gyrus. This altered connectivity profile is consistent with dyslexia-related reading difficulties. 

Dr. John Krystal, Editor of Biological Psychiatry, said, "This study elegantly illustrates the value of functional imaging to map circuits underlying problems with cognition and perception, in this case, dyslexia." 

"As far as we know, this is one of the first studies of dyslexia to examine differences in functional connectivity across the whole brain, shedding light on the brain networks that crucially support the complex task of reading," added Finn. "Compared to typical readers, dyslexic readers had weaker connections between areas that process visual information and areas that control attention, suggesting that individuals with dyslexia are less able to focus on printed words." 

Additionally, young-adult dyslexic readers maintained high connectivity to brain regions involved in phonology, suggesting that they continue to rely on effortful "sounding out" strategies into adulthood rather than transitioning to more automatic, visual-based strategies for word recognition. 

A better understanding of brain organization in dyslexia could potentially lead to better interventions to help struggling readers. 

 Source:Biological Psychiatry

Snail Shells Help Scientists Investigate Rise and Fall of Tibetan Plateau

By using snail shells, a new research has helped scientists investigate the rise and fall of the Tibetan Plateau.

 The rise of the Tibetan plateau, the largest topographic anomaly above sea level on Earth, has been important for both its profound effect on climate and its reflection of continental dynamics. 

Katharine Huntington and colleagues employed a cutting-edge geochemical tool, "clumped" isotope thermometry, using modern and fossil snail shells to investigate the uplift history of the Zhada basin in southwestern Tibet. 

Views range widely on the timing of surface uplift of the Tibetan Plateau to its current high (4.5 km) over more than 2.5 square kilometers. Specifically, interpretations differ on whether the modern high elevations were recently developed or are largely a continuation of high elevations developed prior to Indo-Asian collision in the Eocene. 

Clumped isotope temperatures of modern and fossil snail shells have recorded changing lake water temperatures over the last nine million years. This is a reflection of changes in surface temperature as a function of climate and elevation change. A key to their Zhada Basin paleo-elevation reconstructions is that Huntington and colleagues were able to contextualize them with sampling of modern and Holocene-age tufa and shells from a range of aquatic environments. 

It was found that the Zhada basin was significantly colder from three to nine million years ago, implying a loss of elevation of more than one kilometer since the Pliocene. While surprising given the extreme (4 km) elevation of the basin today, the higher paleo-elevation helps explain paleontological evidence of cold-adapted mammals living in a high-elevation climate, and was probably the local expression of east-west extension across much of the southern Tibetan Plateau at this time. 

Source:The study is published in GSA Bulletin.

 

Health ministers from 11 countries to discuss Ayurveda

Call it a coincidence but within months of the BJP coming to power at the Centre, Ayurveda is set to make a sound at high places as health ministers from the World Health Organisation’s South-East Asia Regional Office (SEARO) will discuss how traditional medicine can be used for healthcare. 

India is the largest nation in this block. The ministers from the WHO’s SEARO region for the first time will deliberate on traditional medicine in a ministerial conference in Dhaka between September 9 and 12. The ministerial consultation will be followed by a global guideline to ensure quality, safety and efficacy.

“Traditional medicine is an important part of health care and mostcountries in the region have their own form of traditional medicines,” said a WHO official.

WHO SEARO comprises 11 nations — Bangladesh, Bhutan, South Korea, India, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand and Timor-Leste. India, being an Asian economic power house, takes a lead in the group on several counts.

The ministerial follows BJP-led NDA government creating an integrated department of Indian systems of medicine in six new All India Institute of Medical Sciences in Bhopal, Patna, Raipur, Bhubaneswar, Rishikesh and Jodhpur.

India has also taken steps to establish a 100-bed hospital on Indian system of medicine – to be called centre of excellence in holistic medicine – and land for medicinal herb cultivation facility for standardised production of medicines. An expert panel has been constituted to recommend a blueprint for the operationalisation of a yoga training and therapy centre at AIIMS Rishikesh.

WHO officials claimed that the thrust on traditional medicine was in accordance with the health agency’s new (2014-23) strategy on traditional medicine to harness its potential contribution to health and universal health coverage.

Even though several WHO technical committees and advisory bodies underscored the importance of the ancient wisdom on healthcare, this is for the first time the ministers would decide how the traditional knowledge can be integrated to the national healthcare delivery system.

WHO director general Margaret Chan and regional head Poonam Khetrapal Singh will be present at the Dhaka meeting that would also seek to prevent harmful use of alcohol, strengthening surgical care and curb the growing threat of viral hepatitis that kill 5 lakh people every year in the region.

Source:DHNS

Location of body fat can increase hypertension risk

Abdominal fat more strongly associated with high blood pressure risk than overall obesity

WASHINGTON (Sept. 1, 2014) — People with fat around their abdominal area are at greater risk of developing hypertension when compared to those with similar body mass index but fat concentrations elsewhere on the body, according to a study published today in the Journal of the American College of Cardiology.
Obesity is a known risk factor for hypertension, or high blood pressure, and it is widely reported that the location of fat on a person's body can lead to increased risk of other health issues like heart disease and cancer. However, the relationship between hypertension and overall obesity versus site-specific fat accumulation is unclear.
For this study, 903 patients enrolled in the Dallas Heart Study were followed for an average of seven years to track development of hypertension. Hypertension was classified as a systolic blood pressure of greater or equal to 140, diastolic blood pressure of greater or equal to 90, or initiation of blood pressure medications. Patients also received imaging of visceral fat, or fat located deep in the abdominal cavity between the organs; subcutaneous fat, or visible fat located all over the body; and lower-body fat.
"Generally speaking, visceral fat stores correlate with the 'apple shape' as opposed to the 'pear shape,' so having centrally located fat when you look in the mirror tends to correlate with higher levels of fat inside the abdomen," said senior author Aslan T. Turer, M.D., M.H.S., a cardiologist at the University of Texas Southwestern Medical Center in Dallas.
At the end of the study period, 25 percent of patients developed hypertension. While higher BMI was associated with increased incidence of hypertension, when abdominal fat content, overall fat content and lower-body fat content were factored in, only abdominal fat remained independently associated with hypertension. The relationship between abdominal fat and hypertension did not change when factoring in gender, age or race.
The strongest correlation between abdominal fat and hypertension was observed with retroperitoneal fat, which is a type of visceral fat located behind the abdominal cavity and largely around the kidneys.
"The high incidence of hypertension and presence of retroperiotoneal fat could suggest that the effects from fat around the kidneys are influencing the development of hypertension," Turer said. "This link could open new avenues for the prevention and management of hypertension. The finding of the fat around the kidney is a novel one and we do not know specifically what the 'in the mirror' correlates are."
Source:Journal of the American College of Cardiology.

Scientists call for investigation of mysterious cloud-like collections in cells

About 50 years ago, electron microscopy revealed the presence of tiny blob-like structures that form inside cells, move around and disappear. But scientists still don't know what they do — even though these shifting cloud-like collections of proteins are believed to be crucial to the life of a cell, and therefore could offer a new approach to disease treatment.
In the Journal of Cell Biology, two researchers are issuing a call to investigators from various backgrounds, from biophysics to cell biology, to focus their attention on the role of these formations— for which they coin a new unifying term "assemblages."
"I want to know what these assemblages are doing in Ewing sarcoma, the disease I concentrate on — and I would think all other researchers who study human biology would want to know their functions in both health and disease," says Jeffrey Toretsky, MD, professor in the department of oncology and pediatrics at Georgetown Lombardi Comprehensive Cancer Center.
So Toretsky partnered with co-author Peter Wright, PhD, professor in the department of integrative structural and computational biology at The Scripps Research Institute in La Jolla, Calif., to pull together all the biophysics and protein biochemistry knowledge available on assemblages into a review article. Toretsky also called on the expertise of chemists and physicists from Georgetown University.
The authors say these assemblages are often, but not always, made up of proteins that are intrinsically disordered, meaning that they do not assume a specific shape in order to fit like a lock and key onto other proteins. These intrinsically disordered proteins seem to find each other and then form into gel-like assemblages — a process called "phase separation" — that can trap and interact with other proteins and even RNA, biological molecules that help decode and regulate genes.
When their work is done — whatever that is — the assemblages dissolve, Toretsky says.
"It is only in the last five years that researchers have begun recognizing that proteins without fixed structures may have important transitional properties that change based upon their local abundance in cells," he says.
Toretsky suspects that if these assemblages play a role in disease, they could be targeted with a small molecule. "Current drug-discovery dogma suggests that it is very hard to make a small molecule to prevent two structured proteins from interacting. However, small molecules have a greater likelihood of disrupting intrinsically disordered protein-protein interactions," he says.
"This review links together very basic biologic phenomena of protein interaction with the potential for new drug discovery," Toretsky says. "It's an exciting challenge."
Source:Journal of Cell Biology