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Friday, November 29, 2013

Diet-Vitamins Potential Damage to Body's Defences



Diet-Vitamins Potential Damage to Body's Defences
Vitamins Potential Damage to Body's Defences
Nov. 26, 2013 — Vitamin supplements are a billion-dollar industry. We want to stay healthy and fit and help our bodies with this. But perhaps we are achieving precisely the opposite?

"We believe that antioxidants are good for us, since they protect the cells from oxidative stress that may harm our genes. However, our bodies have an enormous inherent ability to handle stress. Recent research results show that the body's responses to stress in fact are important in preventing our DNA from eroding. I fear that the fragile balance in our cells can be upset when we supplement our diet with vitamin pills, says Hilde Nilsen to the research magazine Apollon. Nilsen is heading a research group at the Biotechnology Centre, University of Oslo.

Maintenance of genes
Our DNA - the genetic code that makes us who we are - is constantly exposed to damage.
In each of the hundred trillion cells in our body, up to two hundred thousand instances of damage to the DNA take place every day. These may stem from environmental causes such as smoking, stress, environmental pathogens or UV radiation, but the natural and life-sustaining processes in the organism are the primary sources of damage to our DNA.

How can the repair of damage to our DNA help us stay healthy and live long lives?

A small worm provides the answer

To answer this question, Hilde Nilsen and her group of researchers have allied themselves with a small organism - a one millimetre-long nematode called Caenorhabditis elegans (C. elegans). This roundworm, which lives for only 25 days, is surprisingly sophisticated with its 20,000 genes; we humans only have a couple of thousand more.

C. elegans is a fantastically powerful tool, because we can change its hereditary properties. We can increase its ability to repair DNA damage, or we can remove it altogether. We can also monitor what happens when damage to DNA is not repaired in several hundred specimens and through their entire lifespan. Different "repair proteins" take care of various types of damage to the DNA. The most common ones are repaired by "cutting out" and replacing a single damaged base by itself or as part of a larger fragment.

Affecting lifespan with the aid of genes
In some specimens that do not have the ability to repair the damage, the researchers observe that the aging process proceeds far faster than normal. Is it because the damage accumulates in the DNA and prevents the cells from producing the proteins they need for their normal operation? Most researchers have thought so, but Hilde Nilsen doubts it.

One of the genes studied by the researchers has a somewhat shortened lifespan: on average, this mutant lives three days less than normal. Translated into human terms, this means dying at the age of 60 rather than at 70. -"We were surprised when we saw that these mutants do not in fact accumulate the DNA damage that would cause aging. On the contrary: they have less DNA damage. This happens because the little nematode changes its metabolism into low gear and releases its own antioxidant defences. Nature uses this strategy to minimize the negative consequences of its inability to repair the DNA. So why is this not the normal state? Most likely because it comes at a cost: these organisms have less ability to respond to further stress ‒ they are quite fragile.

Hilde Nilsen and her colleagues have now -for the very first time -"shown that this response is under active genetic control and is not caused by passive accumulation of damage to the DNA, as has been widely believed.

This provides an opportunity to manipulate these processes. And that's exactly what we have done: we have re-established the normal lifespan of a short-lived mutant by removing other proteins that repair damage. Hence, the cause could not be accumulation of damage, since there is no reason to assume that a mutant with no other alternative ways to repair its DNA will be less exposed to damage. There must be something else.

The researchers have gone on to discover that this "something else" in fact is the other repair proteins. They believe that the proteins inhibit damage that they fail to repair completely.

The consequence is that they establish a barrier - a road block. This triggers a cascade of signals that reprogram the cell.

Wouldn't this imply that the repair proteins defy their own purpose -"after all, the result is a shorter lifespan?

We need to remember that most likely, the purpose of the DNA repairs is to ensure that we produce healthy offspring -"not necessarily that we live as long as possible after our reproductive age interval. Initiating a survival response that reinforces the antioxidant defences means that a lack of ability to repair the DNA has less impact than it would otherwise have on our reproduction. To the species as a whole, it's a small cost that some individuals will be less good at handling stress and have a shorter life.

Because this is an active process within the cells, the researchers refer to it as reprogramming.

"We have found several proteins that trigger this reprogramming. The process has the same effect as a reduction in caloric intake, which we know helps increase the lifespan in many species. In other words, there are two routes to a long life. When we stimulate both of these two routes in our nematode at the same time, we can quadruple its normal lifespan," Nilsen says.

Can do great harm

The balance between oxidants and antioxidants is crucial to our physiology, but exactly where this equilibrium is situated varies from one person to the next.

"This is where I start worrying about the synthetic antioxidants. The cells in our body use this fragile balance to establish the best possible conditions for themselves, and it is specially adapted for each of us. When we take supplements of antioxidants, such as C and E vitamins, we may upset this balance," the researcher warns.

"It sounds intuitively correct that intake of a substance that may prevent accumulation of damage would benefit us, and that's why so many of us supplement our diet with vitamins. Our research results indicate that at the same time, we may also cause a lot of harm. The health authorities recommend that instead, we should seek to have an appropriate diet. I'm all in favour of that. It's far safer for us to take our vitamins through the food that we eat, rather than through pills," Hilde Nilsen states emphatically.
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Virus- Risk of HIV Treatment Failure Present Even in Those With Low Viral Load



Virus- Risk of HIV Treatment Failure Present Even in Those With Low Viral Load
Risk of HIV Treatment Failure Present Even in Those With Low Viral Load
Nov. 26, 2013 — People with human immunodeficiency virus (HIV) run a higher risk of virologic failure than previously thought, even when their number of RNA copies of the retrovirus per millilitre of blood is slightly above the detection threshold, according to a study by Claudie Laprise at the University of Montreal's Department of Social and Preventative Medicine. Her findings were published in Clinical Infectious Diseases.
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The study was conducted in close collaboration with doctors from the Clinique médicale du Quartier Latin de Montréal, based on data from the files of 1,860 people living with HIV and covering a period of 12 years. Nearly 94% of the patients were men.

Minimizing the presence of the retrovirus The prognosis for people with HIV has considerable improved since the advent of antiretroviral therapy (ART) in 1996. ART acts by reducing the presence of the retrovirus in the blood of infected people. This maintains the immune functions required to prevent the disease from progressing to acquired immunodeficiency syndrome (AIDS). From a clinical point of view, the viral load test measures the activity of HIV in the patient and the effectiveness of ART. The goal of treatment is to keep the viral load below the detection limit, which is about 50 copies of viral RNA/ml.

Reducing the risk of virologic failure Despite treatment, patients sometimes show persistent low viral load during medical follow-up, from 50 to 1,000 copies/ml, for a number of months. The higher the persistent viral loads, the higher the patients are at risk of developing virologic failure. "Virologic failure, defined in this study as a viral load above 1,000 copies/ml of viral RNA in the blood, is to be avoided, not least because it shows the progression of the disease," Laprise explained.

Her results confirm that the risk of virologic failure is a function of persistent viral load. Thus, a patient with a persistent viral load between 500 and 999 copies/ml after a six-month follow-up runs a five times higher risk of virologic failure compared to patients whose viral load is undetectable.

However, a persistent low viral load (50 to 199 copies/ml) doubles this risk as much as an "average" persistent viral load (200 to 499 copies/ml). "This result surprised us because we did not believe that a load as low as 50 to 199 copies/ml after 6 months could result in a significant risk of virologic failure," said Laprise.

According to her, this represents important clinical data: for now, there is still no consensus on the therapeutic way forward in the presence of persistent low viral load. Indeed, in such circumstances, doctors may decide to alter the patient's therapy or continue to observe the patient without changing the therapeutic approach. "To the extent that our results are confirmed by other studies, our findings could provide a new element in assessing the situation of people with HIV, because of the potential risk factors our data have uncovered," Laprise said.
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Cancer-New Agent Against Cancer Cells



Cancer-New Agent Against Cancer Cells
New Agent Against Cancer Cells
Nov. 26, 2013 — Freiburg scientists have discovered a substance that suppresses unchecked cell division in leukemia cells Scientists of the University of Freiburg and the Freiburg University Medical Center from the collaborative research center Medical Epigenetics (SFB 992) have discovered a new active substance that inhibits cell division in leukemia cells and could play an important role in the fight against cancer.
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Junior professor Dr. Stefan Günther was in charge of the research project, which also included research groups participating in SFB 992 Medical Epigenetics led by Prof. Dr. Manfred Jung from the Institute of Pharmaceutical Sciences, Prof. Dr. Oliver Einsle from the Institute of Biochemistry, and Prof. Dr. Roland Schüle from the Freiburg University Medical Center. The team published their findings in the journal Angewandte Chemie International Edition.

The substance XD14 suppresses the function of several proteins from the BET family also known as epigenetic reader proteins: They identify epigenetic changes in so-called histones and pass on this signal, for instance in order to trigger cell division. In the case of leukemia, genetic mutations can cause a disturbance in signaling transduction: The cells continue to divide unchecked, causing damage to the entire organism.

The scientists detected the new agent with a method called virtual screening: The Pharmaceutical Bioinformatics Research Group, headed by Stefan Günther, studied the characteristics of roughly ten million molecules in a computer model. The goal was to identify the few substances whose binding affinity is so great that they can prevent certain proteins of the BET family from passing on signals. The complex calculations involved in this endeavor were made in a computer network maintained by the universities of Baden-Württemberg, the bwGRID. The scientists tested one of the substances on 60 different types of cancer cells. The experiment proved that the agent can significantly suppress cell division in leukemia cells. They are now investigating whether the molecule is suitable for use as a drug.

Around 20 different research groups from the University of Freiburg, the Freiburg University Medical Center, and the Max Planck Institute of Immunobiology and Epigenetics are collaborating on the study of epigenetic mechanisms in SFB 992 in order to develop new strategies for fighting diseases. The DNA stores information on genetic features and passes them on by means of cell division. Epigenetic features, on the other hand, are passed on without being part of the genetic code.
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