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Jan 06
New way of overcoming human stem cell rejection discovered
Biologists have discovered an effective strategy that could prevent the human immune system from rejecting the grafts derived from human embryonic stem cells, a major problem now limiting the development of human stem cell therapies.

The discovery by UC San Diego researchers may also provide scientists with a better understanding of how tumours evade the human immune system when they spread throughout the body.

The study by a collaboration that included scientists from China, was enabled by the development of "humanized" laboratory mice that contained a functional human immune system capable of mounting a vigorous immune rejection of foreign cells derived from human embryonic stem cells.

Because human embryonic stem cells are different from our own body's cells, or "allogenic," a normally functioning human immune system will attack these foreign cells. One way to reduce the body's "allogenic immune response" is to suppress the immune system with immunosuppressant drugs.

The biologists took immune deficient laboratory mice and grafted into their bodies human fetal thymus tissues and hematopoietic stem cells derived from fetal liver of the same human donor. "That reconstituted in these mice a normally functioning human immune system that effectively rejects cells derived human embryonic stem cells," Yang Xu, who headed the team of researchers, said.

With these "humanized" mouse models, the biologists then tested a variety of immune suppressing molecules alone or in combination and discovered one combination that worked perfectly to protect cells derived from human embryonic stem cells from immune rejection.

That combination was CTLA4-lg, an FDA-approved drug for treating rheumatoid arthritis that suppresses T-cells responsible for immune rejection, and a protein called PD-L1 known to be important for inducing immune tolerance in tumours.

The researchers discovered that the combination of these two molecules allowed the allogeneic cells to survive in humanized mice without triggering an immune rejection .

The study was published in the journal Cell Stem Cell.

Jan 06
Indian-American leads new potential treatment for diabetes
In a significant discovery, a team of researchers led by an Indian-American has found that a single gene dysfunction in mice results in developing fasting hypoglycemia, one of the major symptoms of Type 2 diabetes.

The discovery by researchers, led by Prof. Bellur S Prabhakar, focused on a gene MADD for the study and may enable a new potential treatment for diabetes patients.

If MADD is not functioning properly, insulin is not released into the bloodstream to regulate blood sugar levels, said Prabhakar, professor and head of microbiology and immunology at University of Illinois at Chicago.

In previous work, Prabhakar isolated several genes from human beta cells, including MADD, which is also involved in certain cancers. Small genetic variations found among thousands of human subjects revealed that a mutation in MADD was strongly associated with Type 2 diabetes in Europeans and Han Chinese.

People with this mutation had high blood glucose and problems of insulin secretion - the "hallmarks of type 2 diabetes", Prabhakar said.

But it was unclear how the mutation was causing the symptoms, or whether it caused them on its own or in concert with other genes associated with Type 2 diabetes.

To study the role of MADD in diabetes, Prabhakar and his colleagues developed a mouse model in which the MADD gene was deleted from the insulin-producing beta cells. All such mice had elevated blood glucose levels, which the researchers found was due to insufficient release of insulin.

"We didn't see any insulin resistance in their cells, but it was clear that the beta cells were not functioning properly," Prabhakar said.

Examination of the beta cells revealed that they were packed with insulin. "The cells were producing plenty of insulin, they just weren't secreting it," he said.

Prabhakar said that the work shows that Type 2 diabetes can be directly caused by the loss of a properly functioning MADD gene alone.

"Without the gene, insulin can't leave the beta cells, and blood glucose levels are chronically high," he said.

In the future, the researchers plan to look into effects of a drug that allows for the secretion of insulin in MADD-deficient beta cells.

"If this drug works to reverse the deficits associated with a defective MADD gene in the beta cells of our model mice, it may have potential for treating people with this mutation who have an insulin-secretion defect and/or type 2 diabetes," he said.

Type 2 diabetes affects roughly 8 per cent of Americans and over 366 million people worldwide. It can cause serious complications, including cardiovascular disease, kidney failure, loss of limbs and blindness.

Jan 04
Antioxidants in diet linked to cataract risk
Women who eat foods rich in antioxidants may have a lower risk of cataracts as they age, according to a new Swedish analysis.

"Oxidative damage of the eye lens caused by free radicals has been suggested to be crucial in development of cataract," said Susanne Rautiainen of the Institute of Environmental Medicine at the Karolinska Institutet, who led the study.

Her team looked at the diets of more than 30,000 middle aged and older women, and found those with the highest total intake of antioxidants had about a 13 percent lower risk of developing cataracts than women who consumed the least.

"Previous studies have focused on individual antioxidants obtained from the diet or supplements and they have reported inconsistent results," Rautiainen said. "However, in diet much wider ranges of antioxidants are present than those studied previously."

Instead of looking at single antioxidants, such as vitamins C and E, and plant flavonoids such as lycopene, the researchers used a measure of total antioxidant values in foods, which takes into account how the nutrients work together.

For the study, more than 30,000 Swedish women over age 49 were observed for about 7 years for signs of developing cataracts, and were given a dietary questionnaire.

Foods high in antioxidants include coffee, tea, oranges, whole grains and red wine.

Based on total antioxidant consumption, the researchers divided the women into five groups, ranging from the greatest antioxidant intake to the least. Among those who ate the most antioxidants, 745 cases of cataract were recorded, compared to 953 cases among women with the lowest antioxidant consumption.

The results were published in JAMA Ophthalmology.

Women who ate more antioxidants also tended to be more educated and were less likely to smoke.

More than 20 million Americans aged 40 years and older have cataracts, which cause clouded vision and eventually blindness, in one or both eyes, according to the U.S. Centers for Disease Control and Prevention.

"The results are not that surprising," William Christen said.

Christen, of Brigham and Women's Hospital and Harvard Medical School in Boston, studies eye diseases and vitamins and was not involved in the new study.

The findings are in line with previous research suggesting antioxidants may help protect against cataracts, but the study has limitations, he cautioned.

"The women participants simply reported on a questionnaire the food choices they made over the past year," Christen said. "As an observational study, there is always concern that women who choose healthier diets may also differ in other important ways, like body weight, smoking habits, aspects of the diet other than antioxidants, that may be more directly related to cataract risk."

Rautiainen suspects the results would be similar among men and in other countries, but can't say for sure until those studies have been done.

Colorful fruits and vegetables are the best source of antioxidants for people who want to increase their intake, she said.

"Results of numerous observational studies have suggested a possible beneficial role for high antioxidant intake in a number of age-related disorders," Christen said. But in most randomized controlled trials, which would better isolate the effects of antioxidants alone, the link has not held up, he said.

Jan 04
Lentils may be key to beating high blood pressure
Eating a diet packed with lentils can dramatically lower blood pressure levels, a new study has found.

The study from the University of Manitoba in Canada found that adding lentils to the diet can effectively block the increase in blood pressure that occurs with age.

The research, conducted on rats, also found that eating lentils can reverse the changes that occur in blood vessels as a result of high blood pressure.

"These are amazing results, since they provide a non-pharmacological way of treating diseases associated with blood vessel dysfunction," said Dr Peter Zahradka, one of the lead investigators for the study.

The findings are a continuation of two studies published earlier this year, 'the Daily Express' reported.

One of these was a clinical trial which revealed how eating legumes - specifically a mixture of beans, peas, lentils and chickpeas - could improve blood flow to the legs of people with peripheral artery disease.

The second showed that lentils were effective in blocking high blood pressure.

"The most notable finding of the latest study was the fact that lentils could alter the physical properties of blood vessels so that they resembled the vessels found in healthy animals," Zahradka said.

Jan 03
Birth control type tied to time between pregnancies
Women using intrauterine devices (IUDs) and other types of long-term reversible birth control after having a baby are less likely to get pregnant again quickly, a new study suggests.

Women who used those methods were four times more likely to wait more than 18 months between pregnancies compared to those relying on condoms, researchers found.

The World Health Organization endorses a two-year period between birth and a woman's next conception.

Still, one third of all repeat pregnancies in the U.S. occur within 18 months of the previous child's birth. And a growing body of evidence shows this close timing increases the risk a baby will be born early or at a low birth weight.

The time between pregnancies "cannot be explained only by the mother's preferences," Heike Thiel de Bocanegra said.

She and her colleagues from the University of California, San Francisco investigated the link between access to birth control or family planning services and pregnancy spacing.

In the current study of 117,644 California women who'd had at least two children, 64 percent waited 18 months or more between pregnancies and the rest did not.

All women included in the study filed claims through the state's Medicaid program for the poor, called Medi-Cal, or through health providers offering state-funded family planning services.

The researchers matched data on claims for contraceptives to California's birth registry.

"We assumed that access to contraception . . . would improve birth spacing," Dr. Anitra Beasley said.

"This study actually examines this assumption," she said.

Beasley, who studies family planning at Baylor College of Medicine in Houston, was not part of the current research.

Women who used long-acting reversible contraception, including IUDs or implants, were four times more likely to wait at least 18 months to conceive again, compared to those who only used "barrier" contraceptives like condoms or spermicide.

More than half of women started using birth control pills, the ring or the patch after giving birth. They were twice as likely to wait at least 18 months between pregnancies as condom users.

Those relationships stood firm even when the researchers looked at possible influences like the mother's race, education, age and whether she was born in the U.S., according to the report published in the American Journal of Obstetrics and Gynecology.

Women in the study counseled by a certified family planning service provider were 67 percent more likely to wait 18 months between pregnancies, compared with women who utilized Medi-Cal services only.

"Low-income women are sometimes seen only once after giving birth," Thiel de Bocanegra said.

"Some women receive contraception - some do not," she said.

Women in the study received four months worth of covered contraceptives, on average. That number was dragged down by the one third of women in the study who had no contraceptive claims at all.

For Meredith Matone, a researcher with PolicyLab at Children's Hospital of Philadelphia, the study's large size helps build a better understanding of how public health initiatives work in the real world.

"The results we find in clinical trials do not always translate well when implemented on a large scale, where they are subject to challenges that include provider performance, patient compliance and operational hurdles," Matone said.

"Under health care reform, there are opportunities to continue to support such evidence-based public health programs for families," said Matone, who was not involved in the new research.

"Health care providers should know that the optimal pregnancy interval is 18 months or more, and should encourage the use of highly effective contraception during this period," Thiel de Bocanegra said.

"Pediatricians can help, too, by asking the mother what type of contraception she is using," she said.

Jan 03
Relapse of 'cured' HIV patients spurs AIDS science on
Scientists seeking a cure for AIDS say they have been inspired, not crushed, by a major setback in which two HIV positive patients believed to have been cured found the virus re-invading their bodies once more.

True, the news hit hard last month that the so-called "Boston patients" - two men who received bone marrow transplants that appeared to rid them completely of the AIDS-causing virus - had relapsed and gone back onto antiretroviral treatment.

But experts say the disappointment could lay the basis for important leaps forward in the search for a cure.

"It's a setback for the patients, of course, but an advance for the field because the field has now gained a lot more knowledge," said Steven Deeks, a professor and HIV expert at the University of California, San Francisco.

He and other experts say the primary practical message is that current tests designed to detect even very low levels of HIV present in the body are simply not sensitive enough.

As well as having the human immunodeficiency virus (HIV), the Boston patients both also had a type of blood cancer called lymphoma, for which they were treated using bone marrow transplants - one man in 2008 and the other in 2010.

They continued taking the antiretroviral AIDS drugs, but eight months after each patient's transplant, doctors found they could not detect any sign of HIV in their blood.

In the early part of 2013, both patients decided to stop taking their AIDS drugs and both appeared to remain HIV-free - prompting their doctors, Timothy Henrich and Daniel Kuritzkes from Boston's Brigham and Women's Hospital, to announce at a conference in July that they may have been cured.

Yet in December came news that one of the men had begun to show signs of an HIV rebound by August, while the second patient had a relapse in November.

Henrich said the virus' comeback underlined how ingenious HIV can be in finding hiding places in the body to evade attack efforts by the immune system and by drug treatment.

"Through this research we have discovered the HIV reservoir is deeper and more persistent than previously known and that our current standards of probing for HIV may not be sufficient," he said, adding that both patients were "currently in good health" and back on antiretroviral therapy.

INSPIRATION

Barely a decade ago, few HIV scientists would have dared put the words HIV and cure in the same sentence. Yet some intriguing and inspiring cases in recent years mean many now believe it is just a question of time before a cure is found.

First was the now famous case of Timothy Ray Brown, the so-called "Berlin patient," whose HIV was eradicated by a complex treatment for leukemia in 2007 involving the destruction of his immune system and a stem cell transplant from a donor with a rare genetic mutation that resists HIV infection.

Such an elaborate, expensive and life-threatening procedure could never be used as a broad-spectrum approach for the world's 34 million HIV patients. But the results in Brown focused scientific attention on a genetic mutation known as 'CCR5 delta 32' as a target for possible gene therapy treatment.

Then last March, French scientists who followed 14 HIV-positive people known as the "Visconti patients", who were treated very swiftly with HIV drugs but then stopped treatment, said that even after seven years off therapy, they were still showing no signs of the virus rebounding.

That announcement came only weeks after news of the "functional cure" of an HIV-positive baby in Mississippi who received antiretroviral treatment for 18 months from the day she was born. By the time she was two this appeared to have stopped the virus replicating and spreading.

A "functional cure" is when HIV is reduced to such low levels that it is kept at bay even without treatment, though the virus can still be detected in the body.

Sharon Lewin, an HIV expert at Monash University in Australia, said all these developments, as well as the setback suffered by the Boston patients, inspired scientists to investigate many different approaches in the search for a cure.

"We've learnt many things here - and one of the most important is that a tiny, tiny amount of virus can get the whole thing going again," she said. "It's a clear message that we need better ways to pick up the virus."

Scientists are now more convinced than ever that a two-pronged approach which aims to firmly suppress the virus while bolstering the immune system provides the best way forward.

"We need to attack in two ways - reduce the virus to very low levels and also to boost the immune response. We can't do one without the other," said Lewin.

"So we still have to think of other creative ways to control HIV. And it's still early days... before we can say which approach is likely to be the winner."

Jan 02
Antioxidant drug may reverse multiple sclerosis: Study
For people suffering from multiple sclerosis - that affects more than 2.3 million people worldwide - a cure may lie in an antioxidant drug.

Designed by scientists more than a dozen years ago to fight damage within human cells, this drug significantly reversed symptoms in mice that had a multiple sclerosis-like disease.

Researchers led by an Indian-American scientist P. Hemachandra Reddy at the Oregon Health and Science University have discovered that MitoQ -- an antioxidant -- shows some promise in fighting neuro-degenerative diseases.

But this is the first time it has been shown to significantly reverse a multiple sclerosis-like disease in an animal, says the study published in the journal Biochimica et Biophysica Acta Molecular Basis of Disease.

The researchers induced mice to contract a disease called experimental autoimmune encephalomyelitis, or EAE, which is very similar to MS in humans.

After 14 days, the EAE mice that had been treated with the MitoQ exhibited reduced inflammatory markers and increased neuronal activity in the spinal cord - an affected brain region in multiple sclerosis - that showed their EAE symptoms were being improved by the treatment, said the study.

The mice also showed reduced loss of axons, or nerve fibres and reduced neurological disabilities associated with the EAE.

"The MitoQ also significantly reduced inflammation of the neurons and reduced demyelination. These results are really exciting. This could be a new front in the fight against MS," said Reddy, associate scientist at Oregon National Primate Research Centre.

The next steps for Reddy's team is to understand the mechanisms of MitoQ neuroprotection in different regions of the brain.

Multiple sclerosis occurs when the body's immune system attacks the myelin, or the protective sheath, surrounding nerve fibres of the central nervous system. Some underlying nerve fibres are destroyed.

Resulting symptoms can include blurred vision and blindness, loss of balance, slurred speech, tremors, numbness and problems with memory and concentration.

Jan 02
How smokers can stay off ciggies post New Year
Researchers have suggested that smokers should follow a New Year's quit with a weekly recommitment to quit that takes advantage of natural weekly cycles.

In a 2013 study published in JAMA Internal Medicine, researchers from San Diego State University, the Santa Fe Institute, The Monday Campaigns and the Johns Hopkins Bloomberg School of Public Health monitored global Google search query logs from 2008 to 2012 in English, French, Chinese, Portuguese, Russian, and Spanish for searches related to quitting, such as "help quit smoking," to examine weekly patterns in smoking cessation contemplations for the first time.

The study found that people search about quitting smoking more often early in the week, with the highest query volumes on Mondays.

Besides catching smokers' attention on Mondays, weekly cues can help people stay on track with their quit attempts. Since it takes an average of seven to 10 quit attempts to succeed, encouraging people to requit or recommit to their quit attempt once a week can reduce the overall time it takes to quit for good.

Joanna Cohen, a co-author of the Google study and director of the Johns Hopkins Bloomberg School of Public Health Institute for Global Tobacco Control, believes "campaigns for people to quit may benefit from shifting to weekly cues to increase the number of quit attempts participants make each year." In other words, quitters can use Monday as a weekly re-set to make another quit attempt if they slip up.

Morgan Johnson, director of programs and research at the Monday Campaigns and another co-author of the Google paper, said that the surge in quitting contemplations on Monday can be used to provide social support for quitters, an important factor in long-term success.

The study has been published in the Journal of Clinical Psychology.

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